HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_LFS_MB_P

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: BGB IC40 combo (R1)	% inhibition at concentration 5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin combo (R1)
(S)-10-Hydroxycamptothecin	19685-09-7	25.88	47.62	80.409	74.729	89.651	3.229	16.613	20.876	62.792	-13.391	-43.85	-16.014	22.561	-23.455	4.221	-42.455	-19.156
(S)-Crizotinib		-14.51	5.448	30.216	25.647	-60.692	-13.942	-15.503	-10.396	-18.192	7.358	2.155	-10.757	-18.397	17.226	-15.787	-3.955	-27.324
10-Hydroxycamptothecin	19685-09-7	5.42	51.614	69.878	70.548	78.738	-29.387	20.055	-17.064	48.077	-26.831	-25.628	-4.309	0.453	-13.098	-3.991	-15.869	-7.142
2-hexyl-4-Pentynoic Acid	96017-59-3	5.69	-14.193	24.288	-6.707	-9.449	-0.31	-3.528	23.347	3.265	-10.812	-48.614	36.081	-14.841	27.053	3.101	30.158	-10.347
2'-Deoxyuridine	951-78-0	-18.8	-2.022	-29.155	-1.924	-35.512	-20.444	-12.049	-4.819	-37.873	-10.476	-27.133	-29.485	-52.449	-19.56	-7.406	-27.411	-24.723
4-HQN	491-36-1	-17.05	-9.017	-2.055	-25.274	-52.644	7.688	-36.042	1.186	-41.013	-7.417	-44.912	-20.157	-33.145	-2.523	-35.204	-30.486	-32.604
4-iodo-SAHA	1219807-87-0	14.59	76.671	67.985	63.046	112.04	14.384	-17.788	6.722	55.049	-0.131	-50.627	-4.257	-8.645	-17.241	-13.883	-26.373	-24.549
4'-Demethylepipodophyllotoxin	6559-91-7	-9.98	22.527	55.162	5.557	47.977	3.307	-15.657	-1.576	-26.002	-9.718	-10.246	35.153	5.805	23.518	-2.587	7.46	-1.463
4'-Demethylepipodophyllotoxin	6559-91-7	8.43	36.472	2.411	-24.153	29.719	1.112	20.865	-1.067	12.827	2.873	-27.953	-17.014	-21.631	-18.779	-6.868	-20.318	-24.758
5-Azacytidine	320-67-2	-5.82	-8.216	37.162	33.859	15.628	-4.119	-21.448	10.623	-8.345	0.331	17.876	-0.515	4.322	34.147	12.234	6.881	6.465
5-Fluorouridine	316-46-1	-2.55	52.967	32.739	19.627	22.094	21.186	7.564	-17.371	-21.585	-23.991	-35.184	-0.747	-22.383	-8.022	-22.723	-24.208	-21.044
6-Mercaptopurine monohydrate	6112-76-1	-16.66	6.969	-7.611	-34.003	-18.573	0.297	-13.324	-6.931	-46.663	-9.591	-35.983	-13.677	-15.999	-9.641	-9.64	-23.404	-14.71
7-Methylxanthine	552-62-5	-31.24	0.695	-18.692	-48.069	-16.934	-27.976	-21.133	-23.595	-52.25	-21.287	-29.38	-15.507	-10.541	-7.677	-23.78	-24.895	-13.826
8-Azaguanine	134-58-7	-21.29	26.762	4.84	16.385	8.395	-31.288	-13.584	-9.144	-31.148	-14.468	-24.099	-34.554	-13.302	-2.429	-4.531	-36.999	-24.926
A-966492	934162-61-5	19.27	52.936	61.649	58.022	58.1	0.652	0.341	23.264	52.817	12.064	-54.878	1.678	-30.84	12.924	7.364	-24.304	-13.804
Abacavir	136470-78-5	9.78	15.166	29.873	21.809	20.875	26.768	13.496	10.877	-12.019	-8.038	-28.423	-43.311	-34.533	-11.115	-25.316	-37.654	-20.645
ABT-888 (Veliparib)	912444-00-9	-27.24	-17.934	-11.298	-22.125	-58.368	-3.559	-23.869	-27.506	-54.022	-18.942	-21.244	-28.34	-43.036	-0.096	-35.183	-26.771	-39.949
ABT888 hydrochloride	912445-05-7	-25.34	12.674	-21.032	-27.465	-45.023	-11.636	-27.864	-4.89	-56.989	-19.864	-1.889	-28.775	-50.257	-24.9	-15.064	-17.282	-20.321
Aciclovir	59277-89-3	-27.47	-20.576	-23.573	6.218	-19.105	-41.814	-18.729	-14.219	-35.117	-14.605	-16.632	-22.326	-36.115	-11.666	-0.211	-37.24	-7.735
ACY-241	1316215-12-9	-18.4	23	50.294	28.868	99.469	-7.548	-37.904	-13.055	-15.093	6.882	-66.687	-0.542	-35.168	2.276	-0.623	-22.698	-13.131

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：DNA replication ATP-dependent helicase/nuclease DNA2

External ID: CHEMBL4418066

Protocol: N/A

Comment: Target ChEMBL ID: CHEMBL4523236
ChEMBL Target Name: DNA replication ATP-dependent helicase/nuclease DNA2
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: D - Direct protein target assigned
Confidence: Direct single protein target assigned

Data Source: SureChEMBL Patent Bioactivity Data

Standard Type	Standard Units	Activity Comment
Inhibition	%	Not Active
Inhibition	%	Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Active
Inhibition	%	Not Active
Inhibition	%	Active
Inhibition	%	Not Active

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_ICB984_MB

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: BGB IC40 combo (R1)	% inhibition at concentration 5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin combo (R1)
(S)-10-Hydroxycamptothecin	19685-09-7	-30.16	-21.053	-29.778	-18.779	-24.367	-3.007	-20.217	-50.843	-46.577	79.372	91.231	93.852	93.609	9.72	23.172	40.073	38.279
(S)-Crizotinib		-13.11	-10.591	-6.989	-36.008	-41.352	-7.443	-18.037	-13.484	-13.484	51.434	71.109	44.636	42.646	11.829	9.166	-17.767	-21.813
10-Hydroxycamptothecin	19685-09-7	-10.37	2.059	-18.686	14.299	16.682	-35.319	3.33	-4.753	-4.753	87.098	91.403	93.858	93.858	-1.192	34.719	53.713	51.924
2-hexyl-4-Pentynoic Acid	96017-59-3	-6.37	-4.432	-1.863	-21.901	-27.635	5.614	0.477	-17.448	-14.127	-15.335	-13.513	-11.594	-16.015	-9.907	-2.692	-16.001	-19.474
2'-Deoxyuridine	951-78-0	-20.13	-22.046	-1.392	-17.706	-29.372	-19.573	-18.502	-21.219	-21.219	-27.72	-7.407	-21.993	-25.404	3.695	4.002	-31.35	-31.35
4-HQN	491-36-1	-16.45	-4.22	-12.663	-17.838	-22.468	-27.031	-13.759	-12.497	-12.497	-9.481	-1.579	-19.242	-23.528	-5.475	-9.285	-31.775	-36.303
4-iodo-SAHA	1219807-87-0	-43.02	-6.509	-14.494	-32.064	-38.276	-6.97	-33.864	-67.999	-63.248	80.663	76.365	79.607	78.799	-1.936	-14.011	-21.612	-25.254
4'-Demethylepipodophyllotoxin	6559-91-7	-16.77	0.691	-4.061	-31.629	-37.82	6.958	9.155	-43.621	-39.56	4.088	23.993	4.84	1.07	-7.167	12.708	1.809	-1.131
4'-Demethylepipodophyllotoxin	6559-91-7	-19.98	-3.024	-19.379	-8.311	-5.299	-30.79	11.916	-30.516	-30.516	25.556	21.365	20.578	20.578	-13.976	-7.661	-7.755	-11.918
5-Azacytidine	320-67-2	-14.13	-4.383	-16.802	-5.16	-9.292	-8.475	-30.739	-8.654	-8.654	50.182	40.998	64.127	62.837	17.339	3.989	-4.466	-8.055
5-Fluorouridine	316-46-1	-9.47	-6.811	2.891	-14.107	-10.935	-9.054	19.936	-24.371	-24.371	75.993	63.43	86.372	86.372	29.22	26.628	31.987	29.359
6-Mercaptopurine monohydrate	6112-76-1	-13.65	-34.5	-5.753	-6.545	-3.583	-27.381	23.27	-25.237	-25.237	-3.699	-12.181	-14.392	-14.392	-13.502	-10.274	-20.225	-24.87
7-Methylxanthine	552-62-5	-24.86	2.874	-1.563	-16.871	-13.622	-32.069	-1.073	-33.155	-33.155	-4.702	-6.993	-16.677	-16.677	-17.722	-15.317	-28.678	-33.65
8-Azaguanine	134-58-7	-24.99	-12.77	-4.923	-29.209	-42.016	-32.548	-1.681	-32.861	-32.861	6.407	15.798	29.318	27.342	-1.281	-1.816	-9.063	-9.063
A-966492	934162-61-5	-20.72	-6.58	-16.379	-22.917	-28.699	-0.829	-6.458	-39.781	-35.828	41.54	40.263	41.567	39.252	1.102	3.692	-38.772	-42.927
Abacavir	136470-78-5	-19.62	-23.055	-19.265	-34.866	-40.165	-14.82	-29.981	-16.833	-16.833	30.475	26.454	20.878	18.033	13.195	1.069	-26.964	-31.326
ABT-888 (Veliparib)	912444-00-9	-18.66	-10.266	-15.875	-47.323	-53.112	-21.391	-24.945	-14.154	-14.154	-13.711	-25.226	-67.363	-73.38	-9.156	-10.447	-32.943	-37.51
ABT888 hydrochloride	912445-05-7	-15.6	-11.675	-21.802	-45.208	-59.6	-30.315	-24.952	-3.559	-3.559	-12.497	-1.056	-16.011	-19.255	-12.448	0.353	-29.693	-29.693
Aciclovir	59277-89-3	-25.38	-25.92	-35.74	-14.811	-26.19	-28.398	-17.769	-27.67	-27.67	-39.6	-21.409	-33.268	-36.994	-1.033	14.262	-30.6	-30.6
ACY-241	1316215-12-9	-20.1	-20.108	-12.854	-19.251	-24.861	-3.285	-39.353	-20.579	-17.169	41.616	51.457	39.896	37.514	6.258	12.609	-39.219	-43.388

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_HDN33

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin IC20 combo (R1)
(S)-10-Hydroxycamptothecin	19685-09-7	78.66	96.618	98.077	96.549	82.278	82.715	70.973	33.915	61.544	8.956	-34.746	-13.801	-28.741
(S)-Crizotinib		3.71	74.099	54.902	68.748	-0.259	-2.841	14.243	-0.608	-0.224	27.64	-16.565	1.605	35.37
10-Hydroxycamptothecin	19685-09-7	83.46	97.767	98.474	97.993	84.83	84.432	81.131	44.483	67.814	54.783	-13.601	22.397	17.21
2-hexyl-4-Pentynoic Acid	96017-59-3	8.32	-0.563	13.774	-0.039	16.753	10.178	-1.959	11.836	11.132	-3.057	0.318	10.216	3.688
2'-Deoxyuridine	951-78-0	-36.88	-10.084	-20.749	-20.66	-30.663	-38.711	-41.268	-49.186	-21.752	-20.02	-14.553	-33.928	-25.763
4-HQN	491-36-1	-4.24	3.319	-24.365	7.336	8.767	2.056	-23.533	-4.54	11.406	2.752	-25.854	10.061	-1.442
4-iodo-SAHA	1219807-87-0	2.25	96.136	92.726	96.778	-0.589	2.675	4.678	-17.014	-23.14	-14.004	-24.865	-18.746	-5.899
4'-Demethylepipodophyllotoxin	6559-91-7	75.98	77.623	64.545	60.096	92.009	66.89	69.029	12.433	3.419	1.403	8.298	9.828	-0.023
4'-Demethylepipodophyllotoxin	6559-91-7	68.89	81.647	57.769	62.642	87.669	60.394	58.621	0.428	-7.39	2.518	-9.177	-0.377	4.11
5-Azacytidine	320-67-2	3.8	47.827	35.281	38.513	7.836	-3.132	6.682	-2.596	-7.704	-2.771	-16.069	-4.464	-5.5
5-Fluorouridine	316-46-1	71.5	98.083	98.266	97.935	76.469	69.434	68.594	55.597	39.584	40.676	-13.238	-0.714	16.774
6-Mercaptopurine monohydrate	6112-76-1	21.48	55.457	6.401	17.175	34.984	17.633	11.819	4.248	-0.116	7.022	-16.415	-4.595	0.787
7-Methylxanthine	552-62-5	-29.29	-7.59	-14.903	-9.772	-42.96	-37.147	-7.767	-44.835	-26.892	-23.448	-9.578	-30.494	-12.512
8-Azaguanine	134-58-7	-10.24	42.099	20.747	6.449	-12.063	-12.838	-5.816	-36.266	-30.816	-20.763	-24.958	-24.722	-21.496
A-966492	934162-61-5	15.53	54.863	54.34	60.102	13.186	22.58	10.816	-0.604	-4.289	-12.863	6.905	-7.715	-18.04
Abacavir	136470-78-5	-12.21	29.796	3.137	16.88	-10.59	-14.029	-12.011	-18.356	-11.706	6.793	-25.659	-18.362	-17.523
ABT-888 (Veliparib)	912444-00-9	-26.46	-21.756	-41.286	-8.247	-19.697	-35.26	-24.419	-27.909	-22.521	8.163	-26.869	-12.698	-18.289
ABT888 hydrochloride	912445-05-7	-7.62	-0.922	0.864	-1.944	-6.988	-12.66	-3.221	-13.256	-21.822	6.98	-8.834	-17.375	-4.347
Aciclovir	59277-89-3	-44.3	-49.468	-39.606	-30.425	-44.043	-43.99	-44.881	-46.307	-58.486	-50.651	-27.563	-47.959	-35.048
ACY-241	1316215-12-9	18.67	62.062	50.396	56.805	17.43	15.755	22.817	10.327	-18.752	-9.485	3.96	-4.884	-19.154

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：N/A

External ID: CHEMBL1012510

Protocol: N/A

Comment: Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Journal: Antimicrob. Agents Chemother.
Year: 2007
Volume: 51
Issue: 10
First Page: 3688
Last Page: 3698
DOI: 10.1128/aac.00392-07

PubChem Standard Value	Standard Type	Standard Relation	Standard Value	Standard Units	Activity Comment	Data Validity Comment
	IC50				Not Evaluated
	IC50				Not Evaluated
	IC50				Not Evaluated
50	IC50	=	50000	nM
	IC50				Not Evaluated
	IC50				Not Evaluated
72	IC50	=	72000	nM
737	IC50	=	737000	nM		Outside typical range
	IC50				Not Evaluated
	IC50				Not Evaluated
338	IC50	=	338000	nM		Outside typical range
	IC50				Not Evaluated
	IC50				Not Evaluated
	IC50				Not Evaluated
814	IC50	=	814000	nM		Outside typical range
0.04	IC50	=	40	nM

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_HD-MB03

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin IC20 combo (R1)
(S)-10-Hydroxycamptothecin	19685-09-7	99.36	99.925	99.32	99.937	99.27	99.4	99.396	92.453	91.712	89.216	-14.02	29.753	6.971
(S)-Crizotinib		3.43	13.777	0.62	16.106	0.013	-2.986	13.277	-0.971	5.372	0	7.316	-2.236	29.509
10-Hydroxycamptothecin	19685-09-7	99.32	99.886	99.365	99.879	99.331	99.419	99.222	88.597	91.471	89.786	2.385	45.231	23.851
2-hexyl-4-Pentynoic Acid	96017-59-3	3.15	6.65	-2.255	3.134	7.223	0.099	2.135	6.865	-3.217	11.939	-2.83	-1.547	-2.467
2'-Deoxyuridine	951-78-0	-3.73	-25.192	-15.401	4.618	1.963	-8.349	-4.815	-9.828	-5.06	-4.571	-4.725	-7.604	18.613
4-HQN	491-36-1	4.79	-3.106	-12.816	-27.969	-7.853	10.654	11.576	2.488	-7.288	0	0.056	0.63	-12.015
4-iodo-SAHA	1219807-87-0	12.82	99.985	99.961	100.016	13.119	5.056	20.286	-13.44	8.883	1.022	14.607	0.008	1.392
4'-Demethylepipodophyllotoxin	6559-91-7	71.71	91.409	75.725	78.426	81.574	61.861	71.689	7.12	9.567	5.766	-1.542	0.195	-2.861
4'-Demethylepipodophyllotoxin	6559-91-7	69.24	77.31	58.812	71.177	76.676	65.251	65.794	2.96	5.923	7.496	-8.864	-4.008	5.673
5-Azacytidine	320-67-2	2.06	6.15	68.776	50.556	1.381	4.053	0.735	-0.329	7.991	0	-1.582	-10.346	-15.335
5-Fluorouridine	316-46-1	66.94	93.001	84.601	91.115	75.735	71.073	54.011	43.901	47.363	22.999	2.208	-9.424	-3.15
6-Mercaptopurine monohydrate	6112-76-1	-4.55	8.533	3.56	0.212	-3.821	-4.299	-5.536	-0.341	-5.761	-7.182	-0.209	-8.553	9.816
7-Methylxanthine	552-62-5	-10.15	-12.053	-8.618	-9.464	-10.596	-8.647	-11.217	-5.342	6.754	5.577	-5.316	-9.359	-7.175
8-Azaguanine	134-58-7	19.29	76.305	78.106	65.528	22.054	16.072	19.745	-3.789	-4.272	1.783	-5.688	-17.358	12.495
A-966492	934162-61-5	7.06	51.831	47.073	45.843	8.288	1.447	11.446	-6.698	-4.337	-1.193	-9.333	-14.7	-27.527
Abacavir	136470-78-5	-6.69	38.723	35.012	54.051	-5.67	-19.443	5.04	-7.655	-4.278	0	14.388	-17.197	1.107
ABT-888 (Veliparib)	912444-00-9	-8.8	-0.703	-9.125	11.599	-6.536	-16.233	-3.639	2.303	-1.818	0	0.94	-19.432	9.136
ABT888 hydrochloride	912445-05-7	-9.57	-38.022	-5.986	5.306	-8.368	-2.73	-17.611	-10.57	-8.213	-3.419	-7.322	-8.827	-4.195
Aciclovir	59277-89-3	-9.51	-12.297	-20.592	-23.203	-6.973	-2.107	-19.46	-20.619	-10.161	-9.788	-24.232	8.596	-9.363
ACY-241	1316215-12-9	7.2	71.827	90.519	99.191	13.484	-0.477	8.581	-7.718	13.621	17.928	-3.615	-6.41	-21.314

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Severe acute respiratory syndrome coronavirus 2

External ID: CHEMBL4513082

Protocol: N/A

Comment: Target ChEMBL ID: CHEMBL4303835
ChEMBL Target Name: SARS-CoV-2
ChEMBL Target Type: ORGANISM - Target is a complete organism
Relationship Type: N - Non-molecular target assigned
Confidence: Target assigned is non-molecular

Data Source: SARS-CoV-2 Screening Data

Standard Type	Standard Relation	Standard Value	Standard Units
Inhibition	=	0.24	%
Inhibition	=	4.58	%
Inhibition	=	-0.3	%
Inhibition	=	-0.3	%
Inhibition	=	-0.04	%
Inhibition	=	-0.04	%
Inhibition	=	-0.08	%
Inhibition	=	-0.08	%
Inhibition	=	-0.08	%
Inhibition	=	-0.08	%
Inhibition	=	0.03	%
Inhibition	=	0	%
Inhibition	=	0.03	%
Inhibition	=	0	%
Inhibition	=	-0.27	%
Inhibition	=	-0.27	%
Inhibition	=	-0.08	%
Inhibition	=	-0.08	%
Inhibition	=	14.41	%
Inhibition	=	0.39	%

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_CRL2098

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin IC20 combo (R1)
(S)-10-Hydroxycamptothecin	19685-09-7	58.1	80.259	93.494	82.231	48.278	81.919	44.091	37.54	37.54	-43.876	-86.463	-4.869	-77.13
(S)-Crizotinib		-32.45	84.575	72.906	57.071	-12.981	-20.245	-64.113	-2.969	-2.969	23.494	4.825	-41.252	7.955
10-Hydroxycamptothecin	19685-09-7	64.78	88.771	95.261	93.065	64.279	74.548	55.515	47.984	47.984	-11.584	18.572	25.233	-32.529
2-hexyl-4-Pentynoic Acid	96017-59-3	2.92	-0.614	-1.277	18.908	-24.227	26.093	6.9	-10.679	-10.679	29.508	-17.829	-7.762	38.096
2'-Deoxyuridine	951-78-0	-68.33	-16.891	-43.601	-33.918	-84.127	-48.475	-72.381	-8.067	-4.402	-90.526	-61.29	-11.002	-70.711
4-HQN	491-36-1	-61.65	-75.291	-8.497	-63.254	-46.056	-35.46	-103.421	-1.945	-1.945	-42.401	-4.707	-24.691	-1.768
4-iodo-SAHA	1219807-87-0	-40.1	57.842	71.137	59.912	-50.624	-46.144	-23.535	-61.527	-61.527	-92.318	-61.872	-32.064	-60.696
4'-Demethylepipodophyllotoxin	6559-91-7	57.94	67.772	40.386	66.4	66.314	50.299	57.194	-23.767	-23.767	13.014	-10.85	-12.527	36.716
4'-Demethylepipodophyllotoxin	6559-91-7	29.8	52.394	21.828	54.806	54.09	29.765	5.539	12.671	12.671	-51.683	-18.428	3.264	-50.94
5-Azacytidine	320-67-2	-20.99	-1.554	4.229	-13.36	4.626	-8.951	-58.642	-16.371	-16.371	-19.84	-3.052	-3.114	-32.446
5-Fluorouridine	316-46-1	-23.15	35.818	85.456	38.318	-34.691	-14.129	-20.619	12.905	12.905	-3.423	-34.605	0.358	-4.646
6-Mercaptopurine monohydrate	6112-76-1	-2.69	-29.107	-17.021	-6.168	29.119	-5.155	-32.044	-1.351	-1.351	-20.807	-46.41	0.138	-59.214
7-Methylxanthine	552-62-5	-69.2	-40.015	-64.958	-59.135	-27.602	-77.492	-102.498	-13.36	-13.36	-77.664	-43.977	-22.262	-91.474
8-Azaguanine	134-58-7	-27.09	8.309	12.171	18.238	-38.632	-20.745	-21.9	23.787	26.372	-34.23	-56.653	-12.157	-61.378
A-966492	934162-61-5	-18.85	70.709	66.166	46.505	-46.49	-1.164	-8.89	-14.001	-14.001	-28.329	-14.876	-19.111	-45.282
Abacavir	136470-78-5	-21.68	4.937	38.825	22.284	36.68	-23.938	-77.773	-18.479	-18.479	-6.185	-38.088	-33.981	-35.601
ABT-888 (Veliparib)	912444-00-9	-49.77	-28.579	-2.721	-71.642	-27.01	-12.056	-110.254	-36.157	-36.157	7.406	-32.428	-52.846	6.177
ABT888 hydrochloride	912445-05-7	-59.1	-33.448	-14.02	-18.351	-41.191	-70.278	-65.818	42.657	44.602	-33.868	1.165	11.238	-38.67
Aciclovir	59277-89-3	-82.33	-56.449	-73.762	-40.168	-89.159	-65.577	-92.239	-43.359	-38.497	-96.468	-64.403	-26.78	-90.937
ACY-241	1316215-12-9	-36.33	30.264	16.164	35.729	-61.774	-46.499	-0.706	-33.34	-33.34	-3.679	-49.424	5.518	-48.087

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Adenosine receptor A1

External ID: CHEMBL643484

Protocol: N/A

Comment: Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Journal: J. Med. Chem.
Year: 1993
Volume: 36
Issue: 22
First Page: 3341
Last Page: 3349
DOI: 10.1021/jm00074a015

Target ChEMBL ID: CHEMBL318
ChEMBL Target Name: Adenosine A1 receptor
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: H - Homologous protein target assigned
Confidence: Homologous single protein target assigned

PubChem Standard Value	Standard Type	Standard Relation	Standard Value	Standard Units
7	Ki	=	7000	nM
13	Ki	=	13000	nM
9.8	Ki	=	9800	nM
32	Ki	=	32000	nM
10	Ki	=	10000	nM
15	Ki	=	15000	nM
12	Ki	=	12000	nM
6.3	Ki	=	6300	nM
0.014	Ki	=	14	nM
13	Ki	=	13000	nM
12	Ki	=	12000	nM
9.2	Ki	=	9200	nM
0.076	Ki	=	76	nM
0.21	Ki	=	210	nM
4.9	Ki	=	4900	nM
22	Ki	=	22000	nM
33	Ki	=	33000	nM
18	Ki	=	18000	nM
2.5	Ki	=	2500	nM
36	Ki	=	36000	nM

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Severe acute respiratory syndrome coronavirus 2

External ID: CHEMBL4303805

Protocol: N/A

Comment: Target ChEMBL ID: CHEMBL4303835
ChEMBL Target Name: SARS-CoV-2
ChEMBL Target Type: ORGANISM - Target is a complete organism
Relationship Type: N - Non-molecular target assigned
Confidence: Target assigned is non-molecular

Data Source: SARS-CoV-2 Screening Data

Standard Type	Standard Relation	Standard Value	Standard Units	Data Validity Comment
Inhibition	=	-11.52	%	Outside typical range
Inhibition	=	5.09	%
Inhibition	=	-1.71	%
Inhibition	=	3.69	%
Inhibition	=	22.47	%
Inhibition	=	8.51	%
Inhibition	=	-6.86	%
Inhibition	=	-6.18	%
Inhibition	=	-2.07	%
Inhibition	=	3.91	%
Inhibition	=	-5.9	%
Inhibition	=	-2.45	%
Inhibition	=	-5.55	%
Inhibition	=	6.31	%
Inhibition	=	-1.08	%
Inhibition	=	12.7	%
Inhibition	=	0.37	%
Inhibition	=	8.88	%
Inhibition	=	11.63	%
Inhibition	=	-1.96	%

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Replicase polyprotein 1ab

External ID: CHEMBL4495582

Protocol: N/A

Comment: Target ChEMBL ID: CHEMBL4523582
ChEMBL Target Name: Replicase polyprotein 1ab
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: D - Direct protein target assigned
Confidence: Direct single protein target assigned

Data Source: SARS-CoV-2 Screening Data

Standard Type	Standard Relation	Standard Value	Standard Units
Inhibition	=	13.77	%
Inhibition	=	2.35	%
Inhibition	=	21.17	%
Inhibition	=	18.36	%
Inhibition	=	5.381	%
Inhibition	=	18.17	%
Inhibition	=	10.15	%
Inhibition	=	29.56	%
Inhibition	=	18.27	%
Inhibition	=	11.42	%
Inhibition	=	15.4	%
Inhibition	=	7.437	%
Inhibition	=	-3.216	%
Inhibition	=	18	%
Inhibition	=	1.021	%
Inhibition	=	16.4	%
Inhibition	=	2.544	%
Inhibition	=	19.11	%
Inhibition	=	26.15	%
Inhibition	=	5.133	%

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：DNA replication ATP-dependent helicase/nuclease DNA2

External ID: CHEMBL4418065

Protocol: N/A

Comment: Target ChEMBL ID: CHEMBL4523236
ChEMBL Target Name: DNA replication ATP-dependent helicase/nuclease DNA2
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: D - Direct protein target assigned
Confidence: Direct single protein target assigned

Data Source: SureChEMBL Patent Bioactivity Data

Standard Type	Standard Units	Activity Comment
Inhibition	%	Not Active
Inhibition	%	Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Not Active
Inhibition	%	Active
Inhibition	%	Not Active
Inhibition	%	Active
Inhibition	%	Not Active

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Guanine deaminase

External ID: CHEMBL1225633

Protocol: N/A

Comment: Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Journal: Bioorg. Med. Chem.
Year: 2010
Volume: 18
Issue: 18
First Page: 6748
Last Page: 6755
DOI: 10.1016/j.bmc.2010.07.054

Target ChEMBL ID: CHEMBL3129
ChEMBL Target Name: Guanine deaminase
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: H - Homologous protein target assigned
Confidence: Homologous single protein target assigned

PubChem Standard Value	Standard Type	Standard Relation	Standard Value	Standard Units
1.96	Ki	=	1960	nM
1.88	Ki	=	1880	nM
4.44	Ki	=	4440	nM
3.44	Ki	=	3440	nM

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_CRL1545

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis

https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin IC20 combo (R1)
(S)-10-Hydroxycamptothecin	19685-09-7	81.65	99.85	99.893	99.87	74.834	95.285	74.834	4.984	12.482	-19.442	-74.209	-26.958	-81.593
(S)-Crizotinib		-10.04	64.05	63.225	71	-6.275	-14.06	-9.792	7.845	-13.059	-26.77	16.29	-5.961	16.29
10-Hydroxycamptothecin	19685-09-7	82.43	99.94	99.866	99.97	76.734	93.833	76.734	48.473	30.841	48.473	-29.203	12.231	-29.203
2-hexyl-4-Pentynoic Acid	96017-59-3	-23.04	16.34	-30.773	27.75	-12.718	-43.69	-12.718	0.433	-26.609	-25.163	-35.929	0.877	-41.69
2'-Deoxyuridine	951-78-0	-20.7	-14.76	20.793	-26.79	-25.283	-5.718	-31.085	-46.208	21.589	-53.824	-14.716	48.351	-14.716
4-HQN	491-36-1	0.67	-5.49	-9.796	-0.7	4.505	-3.839	1.345	-24.325	-13.775	-71.023	-9.152	6.221	-9.152
4-iodo-SAHA	1219807-87-0	46.94	95.31	92.91	92.55	50.743	39.347	50.743	-7.659	-27.527	-35.335	-94.322	2.354	-102.558
4'-Demethylepipodophyllotoxin	6559-91-7	56.5	83.04	67.209	80.43	57.275	54.955	57.275	-5.66	-31.495	-32.822	-16.242	18.449	-21.169
4'-Demethylepipodophyllotoxin	6559-91-7	47.02	76.16	50.696	50.85	48.603	43.848	48.603	32.185	1.218	32.185	-22.229	-3.917	-22.229
5-Azacytidine	320-67-2	0.69	9.69	0.508	-3.44	-5.274	16.094	-8.758	-10.583	-9.029	-52.118	4.483	0.42	4.483
5-Fluorouridine	316-46-1	82.47	99.74	99.393	99.79	85.076	77.261	85.076	57.753	31.805	57.753	15.879	15.926	15.879
6-Mercaptopurine monohydrate	6112-76-1	-26.27	33.11	6.274	-21.69	-33.991	-10.836	-33.991	2.036	-3.246	2.036	1.202	2.995	1.202
7-Methylxanthine	552-62-5	-15.45	-5.96	5.965	-8.29	-25.557	4.759	-25.557	-33.947	-35.772	-33.947	-60.874	-17.643	-60.874
8-Azaguanine	134-58-7	-20.05	32.49	41.196	1.57	-25.805	-2.709	-31.63	-28.052	4.944	-34.723	-10.571	18.746	-10.571
A-966492	934162-61-5	-0.89	63.38	58.307	66.3	5.815	-14.298	5.815	27.361	-0.352	8.687	-29.387	2.916	-34.871
Abacavir	136470-78-5	-10.81	23.46	13.448	32.26	-12.077	-4.57	-15.786	-25.491	-25.147	-72.627	-3.178	2.134	-3.178
ABT-888 (Veliparib)	912444-00-9	-23.66	-45.68	-16.022	4.27	-18.615	-29.821	-22.54	-19.193	-25.222	-63.963	-38.696	-0.738	-38.696
ABT888 hydrochloride	912445-05-7	9.34	-33.63	48.634	-23.02	20.206	-8.711	16.511	-14.479	7.627	-20.442	5.375	-7.346	5.375
Aciclovir	59277-89-3	-37.74	-38.14	-5.53	-70.04	-44.588	-17.362	-51.284	-59.177	-26.524	-67.469	-24.688	-26.359	-24.688
ACY-241	1316215-12-9	32.29	88.64	90.741	92.93	40.069	16.733	40.069	-5.85	3.899	-33.062	-37.428	15.979	-43.253

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Guanine deaminase

External ID: CHEMBL1225632

Protocol: N/A

Comment: Journal: Bioorg. Med. Chem.
Year: 2010
Volume: 18
Issue: 18
First Page: 6748
Last Page: 6755
DOI: 10.1016/j.bmc.2010.07.054

Target ChEMBL ID: CHEMBL3129
ChEMBL Target Name: Guanine deaminase
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: H - Homologous protein target assigned
Confidence: Homologous single protein target assigned

Standard Type	Standard Units	Activity Comment
Inhibition	%	Active
Inhibition	%	Not Active
Inhibition	%	Not Active

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Histone deacetylase 6

External ID: CHEMBL4808149

Protocol: N/A

Comment: Target ChEMBL ID: CHEMBL1865
ChEMBL Target Name: Histone deacetylase 6
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: D - Direct protein target assigned
Confidence: Direct single protein target assigned

Data Source: Fraunhofer Institute HDAC6 screening

Standard Type	Standard Relation	Standard Value	Standard Units	Data Validity Comment
Inhibition	=	-13.63	%	Outside typical range
Inhibition	=	-37.85	%	Outside typical range
Inhibition	=	-31.68	%	Outside typical range
Inhibition	=	-40.84	%	Outside typical range
Inhibition	=	-33.51	%	Outside typical range
Inhibition	=	-11.71	%	Outside typical range
Inhibition	=	-12.48	%	Outside typical range
Inhibition	=	8.75	%
Inhibition	=	-57.22	%	Outside typical range
Inhibition	=	-43.91	%	Outside typical range
Inhibition	=	-42.06	%	Outside typical range
Inhibition	=	25.26	%
Inhibition	=	31.78	%
Inhibition	=	-63.83	%	Outside typical range
Inhibition	=	1.14	%
Inhibition	=	-17.63	%	Outside typical range
Inhibition	=	14.49	%
Inhibition	=	3.28	%
Inhibition	=	10.08	%
Inhibition	=	13.93	%

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Histone deacetylase 6

External ID: CHEMBL4808150

Protocol: N/A

Comment: Target ChEMBL ID: CHEMBL1865
ChEMBL Target Name: Histone deacetylase 6
ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain
Relationship Type: D - Direct protein target assigned
Confidence: Direct single protein target assigned

Data Source: Fraunhofer Institute HDAC6 screening

Standard Type	Standard Relation	Standard Value	Standard Units
Inhibition	=	-7.39	%
Inhibition	=	-3.08	%
Inhibition	=	97.8	%
Inhibition	=	-9.09	%
Inhibition	=	47.05	%
Inhibition	=	-5.94	%
Inhibition	=	-0.48	%
Inhibition	=	-2.98	%
Inhibition	=	1.42	%
Inhibition	=	12.25	%
Inhibition	=	-2.13	%
Inhibition	=	-4.43	%
Inhibition	=	4.53	%
Inhibition	=	-5.82	%
Inhibition	=	10.36	%
Inhibition	=	-1.3	%
Inhibition	=	12.9	%
Inhibition	=	-3.37	%
Inhibition	=	3.17	%
Inhibition	=	-0.97	%

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：ChEMBL 靶标：Adenosine receptor A2a

External ID: CHEMBL649117

Protocol: N/A

Comment: Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Journal: J. Med. Chem.
Year: 1993
Volume: 36
Issue: 22
First Page: 3341
Last Page: 3349
DOI: 10.1021/jm00074a015

Target ChEMBL ID: CHEMBL2094117
ChEMBL Target Name: Adenosine A2 receptor
ChEMBL Target Type: PROTEIN FAMILY - Target is a group of closely related proteins
Relationship Type: H - Homologous protein target assigned
Confidence: Multiple homologous protein targets may be assigned

PubChem Standard Value	Standard Type	Standard Relation	Standard Value	Standard Units
2.1	Ki	=	2100	nM
11	Ki	=	11000	nM
61	Ki	=	61000	nM
59	Ki	=	59000	nM
31	Ki	=	31000	nM
20	Ki	=	20000	nM
23	Ki	=	23000	nM
16	Ki	=	16000	nM
19	Ki	=	19000	nM
21	Ki	=	21000	nM
0.58	Ki	=	580	nM
4.8	Ki	=	4800	nM
13	Ki	=	13000	nM
26	Ki	=	26000	nM
0.73	Ki	=	730	nM
26	Ki	=	26000	nM
53	Ki	=	53000	nM
14	Ki	=	14000	nM
66	Ki	=	66000	nM
47	Ki	=	47000	nM

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_LFS_MB_2R

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: BGB IC40 combo (R1)	% inhibition at concentration 5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin combo (R1)
BG45	926259-99-6	-19.77	-19.854	-13.395	-3.792	1.585	-25.046	-27.362	-20.367	-6.297	-16.119	-34.066	-33.019	-12.568	-17.129	-24.153	-37.765	-24.607
BGB290	1446261-44-4	-20.2	-17.699	-17.348	-12.56	-24.46	-20.646	-18.811	-23.233	-18.121	-22.357	-20.353	-31.983	-12.249	-18.24	-22.09	-10.623	-15.989
BGP-15	66611-37-8	-16.82	-15.909	-20.09	-18.265	-29.557	-5.283	-20.509	-19.449	-22.057	-10.613	-18.147	26.459	-31.071	-20.249	-21.663	-24.76	-24.619
BIBR 1532	321674-73-1	-3.77	-12.667	-7.673	1.344	6.829	-4.938	-4.895	-6.778	1.515	-1.859	-3.143	-6.759	-3.308	1.086	5.163	-7.773	11.562
BIBR 1532	321674-73-1	-16.34	-15.907	-13.182	-10.857	-4.924	-14.122	-8.268	-28.31	-14.672	-22.253	-22.021	-23.394	-21.884	-15.539	-14.843	42.918	-24.025
Bleomycin Sulfate	9041-93-4	-1.61	-0.884	-11.387	0.518	-27.457	-6.001	-6.407	4.618	1.338	-0.709	6.297	-9.95	-5.673	13.133	-2.06	-2.526	-1.267
BMH-21	896705-16-1	-23.74	-17.821	-7.626	11.969	23.403	-22.534	-15.662	-32.95	-23.824	-25.348	-18.911	-13.927	-27.783	-29.163	-20.304	-17.164	-24.567
BML-210	537034-17-6	-23.49	-22.315	0.256	27.783	7.667	-23.834	-29.125	-3.292	-37.696	-19.595	-32.554	-28.754	-27.144	-8.748	-22.12	-31.572	-24.221
BML-210(CAY10433)	537034-17-6	-15.81	-15.88	-0.615	29.638	25.414	-24.632	-15.807	-12.146	-10.661	-17.072	-12.557	-16.201	-22.618	-12.494	-16.301	-11.501	-19.701
BMS-345541(free base)	445430-58-0	-14.53	-6.522	23.845	47.787	15.929	-11.843	-20.198	-15.777	-10.315	-17.242	-7.057	-19.161	-11.534	-14.417	-12.802	-12.041	-14.272
BRD7716	329059-55-4	-14.46	17.215	55.69	14.769	-6.758	-5.538	-20.956	-14.584	-16.755	-19.374	-21.591	-34.365	-19.6	-19.355	-31.546	-30.607	-21.402
Busulfan	55-98-1	-13.84	26.857	-13.911	-16.716	-4.431	-20.063	-9.993	-6.574	-18.717	-13.54	-6.473	-10.129	-16.903	-13.705	-19.539	-10.162	-28.916
Busulfan	55-98-1	9.5	14.298	-0.087	4.179	9.738	3.549	27.7	12.504	-5.754	-6.503	14.734	-3.457	-14.605	-8.566	23.795	5.097	1.061
Camptothecin	7689-3-4	-4.41	27.892	49.977	78.132	69.236	-27.685	-3.792	-7.221	21.046	-28.096	-12.604	-21.637	-21.792	-14.512	-21.141	-18.982	-18.553
Capecitabine	154361-50-9	-21.14	42.469	-24.543	-24.968	-95.112	-19.452	-21.966	-23.379	-19.749	-29.267	-15.294	-14.668	-21.249	-23.221	-22.746	-17.327	-10.763
Capecitabine	154361-50-9	-14.84	-17.684	-24.018	-16.656	-10.164	-18.206	-8.51	-16.407	-16.252	-18.69	-10.47	-13.104	-7.527	-18.911	-13.637	-13.798	-27.564
Carbenoxolone disodium	7421-40-1	-24.34	-9.978	-20.207	-11.428	-19.189	-23.307	-26.624	-21.109	-26.321	-16.606	-26.187	-26.571	-25.551	-14.42	-33.358	-30.464	-29.437
Carmofur	61422-45-5	-16.73	-19.118	-16.839	-11.397	-25.164	-10.666	-17.036	-22.624	-16.613	-25.197	-16.492	-29.714	-31.018	-17.349	-30.554	-40.797	-31.161
Carmustine	154-93-8	-21.85	-17.147	-31.039	-25.644	-18.262	-22.846	-23.692	-26.349	-14.505	-29.216	-14.706	-25.546	-27.75	-23.452	-19.819	-14.643	-26.484
CAY10603	1045792-66-2	-15.02	36.971	26.219	36.3	69.273	-17.787	-24.163	-16.572	-1.56	-32.313	-29.268	-16.538	-27.255	-11.73	-21.369	-25.498	-28.656

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_UWB1.289

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Data from the primary screen was analyzed using a shiny app developed for this purpose. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments for the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB combo (R1)	% inhibition at concentration 5 uM: Cisplatin combo (R1)	% inhibition at concentration 5 uM (R2)	% inhibition at concentration 5 uM: BGB combo (R2)	% inhibition at concentration 5 uM: Cisplatin combo (R2)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.5 uM (R2)	% inhibition at concentration 0.5 uM: BGB combo (R2)	% inhibition at concentration 0.5 uM: Cisplatin combo (R2)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin combo (R1)	% inhibition at concentration 0.05 uM (R2)	% inhibition at concentration 0.05 uM: BGB combo (R2)	% inhibition at concentration 0.05 uM: Cisplatin combo (R2)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin combo (R1)	% inhibition at concentration 0.005 uM (R2)	% inhibition at concentration 0.005 uM: BGB combo (R2)	% inhibition at concentration 0.005 uM: Cisplatin combo (R2)
(S)-10-Hydroxycamptothecin	19685-09-7	90.14	87.43	82.056	83.076	90.155	74.292	88.111	91.211	90.788	92.567	92.595	83.065	90.623	46.802	43.334	38.368	49.845	17.94	28.678	2.183	-1.181	-12.959	2.992	-6.14	-7.179
(S)-Crizotinib		11.46	55.046	59.176	43.07	60.214	0	0	3.009	25.493	11.291	5.275	3.784	19.905	3.058	22.619	2.628	4.466	17.897	12.788	10.682	7.477	-4.101	6.952	7.298	7.928
10-Hydroxycamptothecin	19685-09-7	89.54	91.653	86.055	85.505	90.265	82.976	88.225	89.822	88.95	91.041	93.321	82.567	91.551	50.592	57.806	48.733	55.779	40.01	40.772	18.829	13.421	7.783	23.616	-2.9	5.272
2-hexyl-4-Pentynoic Acid	96017-59-3	4.47	5.006	21.605	7.522	6.78	2.409	3.709	5.014	15.436	2.836	1.369	3.234	-1.095	-5.011	13.594	15.623	4.705	5.842	2.182	8.299	16.541	3.434	0.459	26.087	24.101
2'-Deoxyuridine	951-78-0	0.16	-13.055	-5.517	12.496	-12.853	-37.314	-19.179	11.025	20.57	8.728	-23.553	0	-15.789	5.16	2.456	1.659	-16.366	-21.027	-1.446	12.68	-3.054	8.759	33.041	-29.096	-17.415
4-HQN	491-36-1	2.5	1.952	3.162	-15.664	-11.141	0	0	13.052	24.901	-7.164	-3.766	1.315	-13.332	13.101	18.157	-7.612	-7.546	-5.205	-17.211	34.764	9.9	-15.699	-5.293	0.952	-18.092
4-iodo-SAHA	1219807-87-0	14.68	84.6	84.515	86.782	70.794	59.316	69.809	15.563	18.262	13.968	15.561	1.786	22.945	-0.849	2.35	-9.379	-17.451	-31.953	-13.191	5.921	22.719	-6.09	-28.172	-42.567	-0.933
4'-Demethylepipodophyllotoxin	6559-91-7	43.98	55.206	47.474	42.089	62.166	26.219	41.396	59.169	33.822	38.147	68.989	18.673	45.058	6.32	13.279	-3.281	-4.245	-0.844	0.424	12.449	21.875	0.287	-17.907	15.298	16.612
4'-Demethylepipodophyllotoxin	6559-91-7	35.93	47.399	44.608	42.919	57.934	16.188	38.041	37.879	22.073	32.549	62.569	15.876	44.648	3.576	9.597	7.55	0.27	8.275	-0.759	7.371	8.931	-2.393	-3.596	-13.569	-6.229
5-Azacytidine	320-67-2	18.42	58.236	49.067	40.966	60.574	0	0	22.515	27.075	15.034	25.49	18.528	1.879	-0.407	16.29	-2.852	0.715	8.021	-5.924	-10.67	-3.468	-9.566	-15.054	10.174	-6.862
5-Fluorouridine	316-46-1	33.46	92.29	90.103	92.488	89.825	80.659	91.339	29.906	29.552	38.888	45.109	18.351	38.93	20.898	16.433	15.506	29.865	-10.944	10.095	12.795	3.971	14.802	-2.237	-16.509	-9.907
6-Mercaptopurine monohydrate	6112-76-1	57.71	59.417	54.195	59.422	74.004	51.804	62.091	64.34	51.779	56.361	73.758	36.843	63.151	10.59	17.583	8.494	-1.196	-14.8	-7.078	3.673	1.535	8.811	-13.103	-18.908	-20.903
7-Methylxanthine	552-62-5	-8.42	23.769	-1.361	2.121	-18.274	-35.54	-23.844	-3.805	-3.863	-1.163	-5.599	-24.309	-11.776	12.406	1.848	-3.135	-8.955	-20.577	-21.432	4.643	9.209	-15.634	-20.186	-9.904	-22.132
8-Azaguanine	134-58-7	32.57	61.804	66.63	63.835	72.391	53.542	64.796	45.359	46.527	41.078	35.944	0	26.515	16.35	16.419	17.851	-6.026	-18.686	7.622	-4.231	16.669	5.119	-9.624	-27.266	-7.56
A-966492	934162-61-5	9.31	42.104	37.238	39.339	58.18	47.02	47.748	26.409	11.309	2.097	11.508	-14.46	19.019	4.622	2.364	-10.504	-17.525	-4.886	-21.59	11.766	12.551	-10.206	-25.901	-25.702	-0.059
Abacavir	136470-78-5	-1.31	33.634	36.435	19.819	20.181	0	0	10.914	13.637	10.586	-4.359	-13.224	-25.421	-1.405	14.356	17.055	-6.26	-7.536	-16.31	-2.261	6.809	-4.285	-17.542	-6.585	-19.912
ABT-888 (Veliparib)	912444-00-9	-9.31	11.488	10.126	-18.345	-2.351	0	0	-2.95	21.656	-10.236	-9.546	-28.777	-25.989	-7.141	19.596	-9.042	-4.52	-8.284	-23.685	-4.796	-0.733	-13.091	-23.523	-10.263	-15.455
ABT888 hydrochloride	912445-05-7	2.13	10.098	8.694	-11.855	7.525	-18.601	-1.056	15.221	12.71	6.209	-7.939	0	-13.441	14.363	10.22	-7.412	-9.38	-16.966	-11.73	5.19	0.123	4.372	-7.171	-25.95	8.238
Aciclovir	59277-89-3	-7.84	-19.992	95.634	-1.757	1.924	71.651	-26.943	-17.704	2.481	-3.824	3.81	0	-31.828	-24.49	-13.453	-15.661	-32.986	-9.007	-11.397	-13.055	-4.466	-9.438	-14.095	-13.974	-29.9
ACY-241	1316215-12-9	8.33	55.771	56.938	55.162	59.458	47.874	60.921	19.384	7.18	3.596	3.691	-8.787	24.905	-9.22	3.759	-15.744	-11.714	-28.253	-17.694	11.491	15.046	3.173	-8.671	-19.035	1.91

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_UWB1.289_BRCA1

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB combo (R1)	% inhibition at concentration 5 uM: Cisplatin combo (R1)	% inhibition at concentration 5 uM (R2)	% inhibition at concentration 5 uM: BGB combo (R2)	% inhibition at concentration 5 uM: Cisplatin combo (R2)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.5 uM (R2)	% inhibition at concentration 0.5 uM: BGB combo (R2)	% inhibition at concentration 0.5 uM: Cisplatin combo (R2)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin combo (R1)	% inhibition at concentration 0.05 uM (R2)	% inhibition at concentration 0.05 uM: BGB combo (R2)	% inhibition at concentration 0.05 uM: Cisplatin combo (R2)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin combo (R1)	% inhibition at concentration 0.005 uM (R2)	% inhibition at concentration 0.005 uM: BGB combo (R2)	% inhibition at concentration 0.005 uM: Cisplatin combo (R2)
(S)-10-Hydroxycamptothecin	19685-09-7	97.13	99.178	96.908	99.83	90.155	74.292	88.111	97.872	107.752	110.883	92.595	83.065	90.623	40.613	49.088	50.655	35.515	21.494	43.166	6.675	7.768	9.586	-13.337	-19.017	-17.378
(S)-Crizotinib		8.71	34.395	53.716	38.784	60.214	0	0	-2.779	12.85	13.237	5.275	3.784	19.905	-4.253	-8.01	15.049	3.342	7.693	14.073	-8.526	-0.878	6.832	9.727	12.261	-25.044
10-Hydroxycamptothecin	19685-09-7	97.8	99.762	98.022	103.689	90.265	82.976	88.225	98.66	107.52	113.166	93.321	82.567	91.551	54.292	51.421	47.383	44.861	36.792	49.959	21.613	22.725	31.273	17.074	4.158	10.28
2-hexyl-4-Pentynoic Acid	96017-59-3	3.74	6.112	-4.847	16.486	6.78	2.409	3.709	6.302	-0.121	12.761	1.369	3.234	-1.095	1.528	-2.579	10.974	6.169	4.62	4.315	1.389	7.166	7.896	3.747	2.105	-9.884
2'-Deoxyuridine	951-78-0	0.57	-15.962	-3.772	10.441	-12.853	-37.314	-19.179	-2.52	17.433	27.864	-23.553	0	-15.789	-3.109	8.695	15.946	9.472	0.462	-11.325	-8.447	-0.8	-5.029	-4.861	-0.126	8.485
4-HQN	491-36-1	0.09	-2.795	11.134	-4.564	-11.141	0	0	-8.409	10.462	14.283	-3.766	1.315	-13.332	-3.714	5.534	6.549	-1.784	19.698	10.128	-6.487	-5.423	14.008	24.347	3.71	-22.3
4-iodo-SAHA	1219807-87-0	7.03	88.307	84.729	104.846	70.794	59.316	69.809	-14.692	-2.537	19.118	15.561	1.786	22.945	-31.155	-10.499	13.351	-7.298	-19.021	-17.557	-43.309	-10.207	6.82	-10.705	-8.135	-21.657
4'-Demethylepipodophyllotoxin	6559-91-7	51.57	72.113	55.281	64.063	62.166	26.219	41.396	78.99	48.292	49.427	68.989	18.673	45.058	4.224	11.809	2.296	0.214	4.916	7.983	0.84	11.206	12.36	0.536	-1.403	-2.552
4'-Demethylepipodophyllotoxin	6559-91-7	46.71	72.19	54.803	63.112	57.934	16.188	38.041	73.821	35.709	47.641	62.569	15.876	44.648	9.388	13.165	10.289	4.924	2.359	22.985	0.04	13.813	27.752	10.665	-3.429	-2.416
5-Azacytidine	320-67-2	20.66	68.813	63.391	51.033	60.574	0	0	27.839	19.367	30.854	25.49	18.528	1.879	-14.309	-15.93	24.076	61.599	-1.651	-22.714	-31.707	-12.776	6.66	-12.011	12.314	-30.568
5-Fluorouridine	316-46-1	40.63	105.932	110.477	118.408	89.825	80.659	91.339	60.77	47.769	32.833	45.109	18.351	38.93	39.161	33.289	23.573	60.491	20.898	20.458	-3.413	12.773	10.8	17.081	4.316	-11.087
6-Mercaptopurine monohydrate	6112-76-1	63.59	97.098	95.684	100.095	74.004	51.804	62.091	80.859	54.578	72.346	73.758	36.843	63.151	0.97	9.893	20.659	7.273	5.701	10.876	-0.735	-1.643	30.676	1.871	-5.751	-0.677
7-Methylxanthine	552-62-5	-8.08	-2.11	-2.145	4.946	-18.274	-35.54	-23.844	-3.417	11.145	-14.506	-5.599	-24.309	-11.776	-8.82	13.162	10.413	-14.741	8.813	-11.715	-6.318	4.276	28.856	-6.972	-10.691	-27.266
8-Azaguanine	134-58-7	38.26	85.506	85.109	92.105	72.391	53.542	64.796	55.732	50.607	60.753	35.944	0	26.515	10.269	12.382	11.48	-15.818	13.294	-2.217	-7.604	-2.676	11.699	-3.15	-2.006	-11.242
A-966492	934162-61-5	12.53	57.704	55.745	69.86	58.18	47.02	47.748	18.039	25.021	16.08	11.508	-14.46	19.019	9.811	-1.531	22.943	5.954	5.191	11.041	4.019	10.509	13.436	3.053	-7.191	3.111
Abacavir	136470-78-5	-4.62	76.018	44.065	67.628	20.181	0	0	-2.169	9.211	8.247	-4.359	-13.224	-25.421	-9.861	-1.775	19.014	10.284	11.477	-20.996	-13.42	-7.668	-9.038	1.501	1.773	-37.871
ABT-888 (Veliparib)	912444-00-9	-7.22	-11.984	10.194	-4.845	-2.351	0	0	-9.527	10.499	20.016	-9.546	-28.777	-25.989	-10.547	-5.802	19.983	-3.062	-0.165	-11.663	-17.764	0.809	2.625	4.864	-9.08	-8.569
ABT888 hydrochloride	912445-05-7	-0.79	-14.077	-0.186	4.222	7.525	-18.601	-1.056	-1.282	10.762	7.159	-7.939	0	-13.441	1.223	2.926	3.802	-3.157	1.318	-19.035	-4.204	-9.975	2.9	6.131	17.11	-3.928
Aciclovir	59277-89-3	-9.4	-34.517	-23.093	-14.764	1.924	71.651	-26.943	-13.49	-13.583	-1.294	3.81	0	-31.828	-21.256	-10.182	-10.185	2.044	-18.155	-22.681	-15.151	-13.333	-7.128	-2.314	-11.963	-28.024
ACY-241	1316215-12-9	15.14	73.108	70.472	82.968	59.458	47.874	60.921	10.204	18.615	42.237	3.691	-8.787	24.905	0.847	3.639	9.168	2.513	22.638	6.993	7.095	16.106	20.586	-0.034	22.495	15.011

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：24983 靶标：Huntingtin

External ID: KUHTS-Muma KU-CaM-Htt INH-01

Protocol: 1; Dispense 45 nl compounds (10 mM stocks) using ECHO 555 to Alpha 384 well assay plates. Dispense 45 nl DMSO to control columns 1 and 2 of 384 well plates.
2; Incubate 5 ul of 6XHis-mHTT (Final, 13 nM) with the compounds for 40 mins at room temperature in buffer containing 10 mM Tris.HCl pH 7.4, 1 mM calcium chloride, 150 mM sodium chloride, 0.1% BSA and 20% glycerol.
3; Dispense 5 ul of 6XGST-CaM (Final 13 nM) in buffer A.
4; Incubation; 1 hour (dark at 25C)
5; Dispense 20 ul of Nickel chelate acceptor beads (Final, 20 ugs/ml) and Glutathione donor beads (Final, 30 ugs/ml). Incubate for 2h, room temperature.
6; Detector: Perkin Elmer Enspire, Alphascreen Module (Excitation 680nm/Emission 570nm).

NOTES (numbers refer to Sequence numbers above)
1. Alphascreen bead incubations were performed in green light, TiterTek setting 400rpm.
2. All incubation and addition steps were followed by mixing and centrifugation at 400g,1 min.
3. The percent inhibition for each compound was calculated as follows:
100- [100 *((Test Compound-Median Low Control) / (Median High Control - Median Low Control))]

Where:
Test_Compound is defined as wells containing His mHTT + GST CaM in the presence of test compound

High_Control is defined as wells containing His mHTT + GST CaM and DMSO.

Low_Control is defined as wells containing His mHTT and DMSO.

Comment: All percent inhibition data reported were normalized to high and low controls on a per-plate basis. The results of primary screening data include compounds contributing to assay signal interference, interference with tags binding to Alpha beads, chelators, process related artifacts etc.. The actives were defined as compounds that inhibited Alphascreen reads to greater than 50%.

Activity at 15 uM	Phenotype
-3.1
4.2
-4.8
-0.6
-3.9
-6
75.3	Inhibitor
-10.3
-7
-2
-3.8
17.6
-4.8
-4.1
-7.8
-7.5
15.2
7.8
-2.5
-13.4

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_BT084_ICGC_MB145

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: BGB IC40 combo (R1)	% inhibition at concentration 5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: BGB IC40 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin combo (R1)
(S)-10-Hydroxycamptothecin	19685-09-7	13.4565	42.331	18.747	46.864	27.957	-1.345	15.887	-7.614	46.898	-29.134	-47.166	-21.818	12.76	-16.209	42.504	-72.195	-7.069
(S)-Crizotinib		5.09725	55.813	97.615	83.347	96.484	-0.516	23.968	2.823	-5.886	-6.51	2.907	-35.89	-4.938	-8.898	-14.258	32.663	-7.115
10-Hydroxycamptothecin	19685-09-7	7.412	44.749	51.014	63.405	7.98	3.367	-9.831	-19.197	55.309	-24.058	-34.887	-8.974	1.876	-9.4	1.74	1.027	5.539
2-hexyl-4-Pentynoic Acid	96017-59-3	8.5895	14.367	-31.682	72.281	1.82	-2.277	0.631	26.229	9.775	-2.995	6.66	2.202	13.864	-5.1	26.352	-3.269	-3.106
2'-Deoxyuridine	951-78-0	-24.58575	-10.582	5.163	-3.114	1.736	-5.852	-30.931	-61.187	-0.373	4.307	-6.399	26.551	4.306	-10.991	0.135	-39.496	1.392
4-HQN	491-36-1	-14.001	12.228	-15.839	28.331	-11.795	-12.776	5.548	0.622	-49.398	-2.264	3.988	-51.663	-23.157	-18.58	-31.904	2.541	-26.923
4-iodo-SAHA	1219807-87-0	12.20575	103.109	53.844	74.477	104.77	23.933	-0.305	-4.45	29.645	-3.678	-52.617	-26.056	8.836	-27.111	-24.404	11.158	-0.204
4'-Demethylepipodophyllotoxin	6559-91-7	23.08125	73.203	26.065	86.565	43.389	24.873	37.621	30.436	-0.605	16.975	13.356	7.154	21.808	-7.533	-2.339	-27.433	-14.279
4'-Demethylepipodophyllotoxin	6559-91-7	7.9725	24.93	20.106	30.92	22.472	17.255	12.515	-2.485	4.605	-1.009	-30.383	-9.477	-11.329	-2.846	-29.814	-1.937	-3.605
5-Azacytidine	320-67-2	10.945	8.496	13.919	78.994	53.945	-4.734	21.846	35.624	-8.956	2.728	2.791	30.699	6.48	0.67	0.118	29.17	-10.85
5-Fluorouridine	316-46-1	-22.8525	11.926	5.372	8.791	-1.49	-20.931	-49.46	-2.572	-18.447	10.239	-11.987	2.241	-49.211	-10.826	-41.378	6.304	-33.181
6-Mercaptopurine monohydrate	6112-76-1	-23.32475	-10.05	24.862	21.291	-59.744	-15.369	-27.672	-22.274	-27.984	-9.45	-22.412	-9.265	-51.996	-8.99	-28.912	10.638	-11.769
7-Methylxanthine	552-62-5	-17.3125	-30.358	-26.505	-17.228	-68.058	-9.05	-35.548	-17.432	-7.22	-5.357	-39.87	-20.554	-48.973	-19.477	19.373	10.336	-3.012
8-Azaguanine	134-58-7	-31.98075	6.118	15.406	6.338	22.559	1.796	-69.516	-56.984	-3.219	1.925	66.312	-14.038	-1.187	-19.869	-25.702	-22.741	-6.642
A-966492	934162-61-5	-17.3975	45.001	17.714	42.489	41.768	9.47	-41.47	-30.459	-7.131	11.519	-79.942	14.698	-5.741	-9.987	-17.764	-63.952	-13.156
Abacavir	136470-78-5	-11.9045	30.51	34.713	47.836	36.51	4.568	7.188	-28.773	-30.601	-9.087	-1.415	-24.442	-5.391	-10.566	-4.507	-22.93	-4.461
ABT-888 (Veliparib)	912444-00-9	-14.12825	-8.418	8.926	62.943	2.984	-2.746	1.481	-17.333	-37.915	-4.29	9.888	13.557	-19.554	-11.29	-12.886	-13.909	9.809
ABT888 hydrochloride	912445-05-7	-22.04625	-18.474	-22.025	5.682	-9.136	-10.165	-33.521	-22.936	-21.563	-11.764	-23.317	2.756	-14.272	-23.077	-11.496	-36.754	-11.712
Aciclovir	59277-89-3	-21.3095	-0.642	-25.421	34.677	-6.786	-2.894	-28.814	-41.055	-12.475	-7.37	-14.769	-1.079	-11.68	-13.87	-3.041	-6.226	1.333
ACY-241	1316215-12-9	2.48275	65.032	16.993	57.369	78.882	20.18	-10.183	-7.275	7.209	9.422	-61.137	-0.825	-13.573	-2.867	-15.328	-50.949	-19.999

HepG2 Cytotoxicity Assay Measured in Cell-Based System Using Plate Reader - 7071-02_Inhibitor_Dose_DryPowder_Activity_Set16

来源：25008 靶标：N/A

External ID: DKFZ_drug_screen_chromothripsis_Human_astrocytes

Protocol: For each cell line included in the screen (UWB1.289, UWB1.289+BRCA1, MDA-MB-436, HD-MB03, HD-N33, normal human astrocytes, SaOS-2, KHOS-240S, SJSA-1, LFS_MB_P (primary tumor), LFS_MB_1R (first relapse), LFS_MB_2R (second relapse), RCMB18, BT084 and ICB984) the IC20 and IC40 values of BGB 290 (Pamiparib, MedChemExpress, HY-104044) and cisplatin (MedChemExpress, HY-17394) were determined. The 375 compounds from 2 drug libraries, namely TargetMol (Catalog No. L3900) and DiscoveryProbe (ApexBio, L1033) were diluted in 96-well plates to achieve final concentrations of 5 microM, 0.5 microM, 0.05 microM and 0.005 microM. Cells were then seeded at optimized densities. Each cell line or tumor entity was treated with its respective IC20 concentration of BGB 290 or cisplatin. Spheroids from patient-derived xenograft models were treated with both IC20 and IC40 of BGB 290. Cells were incubated at 37 degrees C for 96 hours. The metabolic activity was measured after 96 hours with the ATPlite assay (Perkin Elmer, 6016947). Values from the blank measurements were subtracted from the treatment wells and normalized to the vehicle controls. 10% DMSO treatment was used as positive control as measure of 100% metabolic inhibition whereas vehicle DMSO concentration was used as negative control as measure of 0% metabolic inhibition. The effect of single treatments was compared to the combination treatments to identify drugs that have potential additive or synergistic effects with BGB-290 or cisplatin or both. CART (https://cart.embl.de/) was used to match chemicals to Pubchem identifiers and for drug-annotation enrichment analysis. Compounds were scored as active in Pubchem if the average cell metabolic activity inhibition is at least 80% in single or combination treatments at the 0.5 uM concentration.

Comment: A synergistic interaction between HDAC- and PARP inhibitors in childhood tumors with chromothripsis
https://www.biorxiv.org/content/10.1101/2021.04.22.440879v1

Chemical Name	PUBCHEM_EXT_CAS_Number	% average inhibition at concentration 0.5 uM in single/combination treatments	% inhibition at concentration 5 uM (R1)	% inhibition at concentration 5 uM: BGB IC20 combo (R1)	% inhibition at concentration 5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.5 uM (R1)	% inhibition at concentration 0.5 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.5 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.05 uM (R1)	% inhibition at concentration 0.05 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.05 uM: Cisplatin IC20 combo (R1)	% inhibition at concentration 0.005 uM (R1)	% inhibition at concentration 0.005 uM: BGB IC20 combo (R1)	% inhibition at concentration 0.005 uM: Cisplatin IC20 combo (R1)
(S)-10-Hydroxycamptothecin	19685-09-7	84.09	95.564	85.192	89.979	84.695	91.608	75.959	71.039	53.263	38.323	40.691	42.878	15.598
(S)-Crizotinib		-2.23	53.665	23.154	9.081	3.462	-5.883	-4.276	19.57	9.383	16.757	7.297	8.033	9.039
10-Hydroxycamptothecin	19685-09-7	83.33	96.564	83.979	90.743	83.481	86.079	80.44	68.011	55.16	40.681	30.12	34.155	18.784
2-hexyl-4-Pentynoic Acid	96017-59-3	6.72	4.936	-10.752	-14.766	-9.773	20.477	9.453	2.709	0.763	-2.46	4.107	-4.201	4.478
2'-Deoxyuridine	951-78-0	3.18	-14.947	4.155	-0.637	11.915	-6.853	4.489	3.508	3.508	18.344	25.211	-1.683	5.812
4-HQN	491-36-1	12.47	13.764	2.958	13.617	16.899	-1.334	21.844	17.705	12.803	13.573	2.727	19.12	11.615
4-iodo-SAHA	1219807-87-0	29.2	99.557	101.437	99.612	35.814	30.475	21.297	12.338	-9.21	8.772	27.084	-15.709	0.936
4'-Demethylepipodophyllotoxin	6559-91-7	69.7	84.598	70.843	66.249	79.982	66.61	62.496	18.106	-4.868	12.537	12.354	-3.473	8.429
4'-Demethylepipodophyllotoxin	6559-91-7	62.36	87.933	74.777	72.427	77.594	57.089	52.388	4.897	1.565	21.31	2.674	-10.69	10.841
5-Azacytidine	320-67-2	13.15	59.91	40.361	42.915	10.543	17.739	11.182	21.51	22.071	18.248	14.85	-27.596	-7.333
5-Fluorouridine	316-46-1	57.3	87.665	73.157	69.77	76.788	56.249	38.868	69.361	38.278	43.188	20.815	9.425	6.383
6-Mercaptopurine monohydrate	6112-76-1	13.81	24.216	14.485	-5.858	23.844	14.17	3.426	18.608	3.436	17.549	15.981	-6.949	11.664
7-Methylxanthine	552-62-5	13.99	9.564	1.677	-6.577	19.72	17.864	4.381	-1.197	-5.312	4.473	19.113	6.708	10.061
8-Azaguanine	134-58-7	3.68	20.574	17.914	-4.109	4.091	0.254	6.708	4.876	4.876	20.878	25.04	-2.76	-1.358
A-966492	934162-61-5	18.26	59.302	50.503	50.076	10.332	32.477	11.966	27.41	-1.52	13.917	20.222	0.542	10.849
Abacavir	136470-78-5	11.53	42.485	25.857	33.642	16.313	10.049	8.232	15.919	7.072	9.999	22.728	4.208	14.543
ABT-888 (Veliparib)	912444-00-9	9.85	24.096	1.572	11.34	21.263	-1.527	9.802	15.373	17.216	-1.385	21.13	2.628	3.809
ABT888 hydrochloride	912445-05-7	-2.9	4.238	1.362	-32.395	10.202	-5.783	-13.118	1.662	1.662	-2.166	26.006	3.733	-1.752
Aciclovir	59277-89-3	-9.43	-3.974	10.429	-63.254	3.717	-2.387	-29.62	4.374	4.374	-3.689	-7.337	-3.912	-18.399
ACY-241	1316215-12-9	10.68	67.186	60.001	42.419	6.284	11.746	14.001	13.333	-3.989	4.388	21.507	3.438	11.666

552-62-5 靶点实验数据