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

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

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

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

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

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

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

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

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

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

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