THZ531
Modify Date: 2025-09-10 23:09:19
THZ531 structure
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Common Name | THZ531 | ||
|---|---|---|---|---|
| CAS Number | 1702809-17-3 | Molecular Weight | 558.07 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C30H32ClN7O2 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of THZ531THZ531 is a covalent inhibitor of both CDK12 and CDK13 with IC50s of 158 nM and 69 nM, respectively. |
| Name | THZ-531 |
|---|---|
| Synonym | More Synonyms |
| Description | THZ531 is a covalent inhibitor of both CDK12 and CDK13 with IC50s of 158 nM and 69 nM, respectively. |
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| Related Catalog | |
| Target |
CDK12:158 nM (IC50) CDK13:69 nM (IC50) |
| In Vitro | The results from Kinase assays demonstrate that THZ531 potently inhibits CDK12 and CDK13 with IC50s of 158 nM and 69 nM, respectively; whereas inhibition of CDK7 and CDK9 is more than 50-fold weaker with IC50s of 8.5 and 10.5 µM, respectively. THZ531 treatment leads to a dramatic and irreversible decrease in Jurkat cell proliferation with an IC50 of 50 nM. FACS cell cycle analysis following treatment with escalating doses of THZ531 displays a dose and time-dependent increase in the number of cells exhibiting sub-G1 content. At 50 nM THZ531, no increase in the percentage of apoptotic cells is observed over DMSO control for the time course of the experiment. Higher doses of THZ531 leads to pronounced Annexin V signal with 30 to 40% annexin V-positively stained cells by 72 hrs. A dramatic reduction in elongating Pol II following THZ531 treatment is also observed[1]. |
| Kinase Assay | Cells are treated with THZ531 or DMSO for 6 hrs. Following treatment cells are washed 2-fold with cold PBS and then lysed in the following lysis buffer: 50 mM Hepes pH 7.4, 150 mM NaCl, 1% Nonidet P40 substitute, 5 mM EDTA, 1 mM DTT, and protease/phosphatase cocktails. Following clearance, lysates are treated with bio-THZ1 or bio-TH531 for pulldown overnight at 4°C. Lysates are further incubated at room temperature for 3 hrs to increase the efficiency of covalent bond formation. Lysates are then incubated with streptavidin agarose for pulldown for an additional 2 to 3 hrs at 4°C[1]. |
| Cell Assay | Jurkat cells are plated in 96-well plates at 20,000 cells/well in fresh media and treated with THZ531 or DMSO at the indicated concentrations for 72 hours. HAP1 cells are seeded in 96-well plates at 12,000 cells/well in fresh media and 24 hours later are treated with THZ531 at the indicated concentrations for 72 hours. Anti-proliferative effect of THZ531 is assessed. To assess the effect of inhibitor washout on anti-proliferation of Jurkat cells, cells are treated with THZ531 or DMSO for 6 hrs. Inhibitor-containing medium is then removed and incubated with or without THZ531 for 66 hrs. Anti-proliferative effect of THZ531 is assessed. All proliferation assays are performed in biological triplicate. IC50s are determined using non-linear regression curve fit[1]. |
| References |
| Molecular Formula | C30H32ClN7O2 |
|---|---|
| Molecular Weight | 558.07 |
| InChIKey | RUBYHLPRZRMTJO-MOVYNIQHSA-N |
| SMILES | CN(C)CC=CC(=O)Nc1ccc(C(=O)N2CCCC(Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1 |
| Storage condition | 2-8℃ |
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Name: Inhibition of CDK12 (unknown origin) at 1 uM in presence of ATP by kinase-glo plus lu...
Source: ChEMBL
Target: Cyclin-dependent kinase 12
External Id: CHEMBL5626381
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Name: Inhibition of CDK7 (unknown origin)
Source: ChEMBL
Target: Cyclin-dependent kinase 7
External Id: CHEMBL4611854
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Name: Inhibition of PARP1 (unknown origin) at 1 uM incubated for 1 hr by ELISA analysis rel...
Source: ChEMBL
Target: Poly [ADP-ribose] polymerase 1
External Id: CHEMBL5626382
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Name: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) pre incubated up to 60 mins follow...
Source: ChEMBL
Target: CDK-activating kinase assembly factor MAT1
External Id: CHEMBL4611857
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Name: Inhibition of CDK12 (unknown origin) in presence of ATP by kinase-glo plus luminescen...
Source: ChEMBL
Target: Cyclin-dependent kinase 12
External Id: CHEMBL5626383
|
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Name: Inhibition of CDK2/Cyclin A (unknown origin)
Source: ChEMBL
Target: Cyclin-A2
External Id: CHEMBL4828798
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Name: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate prei...
Source: ChEMBL
Target: Cyclin-dependent kinase 12
External Id: CHEMBL5538676
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Name: Cytotoxicity counterscreen for inhibitors of SARS-CoV-2 cell entry
Source: NCGC
Target: N/A
External Id: TRND-SARS-CoV-2-cytotox-48hr
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Name: Protac activity at human CDK12/CycK in human MDA-MB-231 cells assessed as downregulat...
Source: ChEMBL
Target: Cyclin-dependent kinase 12
External Id: CHEMBL5043525
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Name: Primary qHTS to identify inhibitors of SARS-CoV-2 cell entry
Source: NCGC
External Id: TRND-SARS-CoV-2-PP
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| THZ531 |