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Formula | C17H19FN4O2S |
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Molecular Weight | 362.42 | CAS No. | 860352-01-8 | |
Solubility (25°C)* | In vitro | DMSO | 73 mg/mL (201.42 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | AZD7762 is a potent and selective inhibitor of Chk1 with IC50 of 5 nM in a cell-free assay. It is equally potent against Chk2 and less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. Phase 1. | ||||
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In vitro | AZD7762, a more selective Chk1 inhibitor, inhibits Chk1 phosphorylation of a cdc25C peptide by reversibly binding to the ATP-binding site of Chk1, with IC50 of 5 nM and Ki of 3.6 nM. AZD7762 induces cell arrest with EC50 of 0.620 μM, and significantly abrogates the camptothecin induced G2 arrest with an EC50 of 10 nM, by blocking the chk1 dependent degradation of Cdc25A and activation of Cyclin A. AZD7762 (300 nM) enhances the antitumor efficacy of against SW620 and against MDA-MB-231 by reducing the GI50 values from 24.1 nM and 2.25 μM to 1.08 nM and 0.15 μM, respectively. [1] AZD7762 shows cytotoxicity against a variety of neuroblastoma cell lines bearing p53 wild type, p53 mutation, Mdm2 amplification or p14 deletion with IC50 values ranging from 82.6-505.9 nM. [2] |
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In vivo | AZD7762 alone at 25 mg/kg shows little antitumor activity in the H460-DNp53 xenograft mice and SW620 xenograft mice, but when administrated in combination, AZD7762 shows significant antitumor efficacy in the two xenografts mice with a log cell kill of 0.9 or percent treated/control (%T/C) of 26 even at low dose of 12.5 mg. Dosing of AZD7762 in combination in the H460-DNp53 xenograft rat inhibits the tumor volume in a dose-dependent manner with the %T/C values of 48 and 32 for 10 and 20 mg/kg AZD7762, respectively. AZD7762 (25 mg/kg) in combination causes complete tumor regression in the SW620 xenograft mice with the %T/C increasing significantly to -66% and -67%, respectively. [1] |
Kinase Assay: |
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Cell Assay: |
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Animal Study: |
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Data from [Cancer Discov, 2012, 2, 524-39]
Data from [Cancer Biol Ther, 2012, 13]
Data from [Cancer Biol Ther, 2012, 13]
Data from [Cancer Biol Ther, 2011, 12, 215-28]
The MYCN oncoprotein is an RNA-binding accessory factor of the nuclear exosome targeting complex [ Mol Cell, 2024, S1097-2765(24)00285-5] | PubMed: 38703770 |
Natural pentacyclic triterpenoid from Pristimerin sensitizes p53-deficient tumor to PARP inhibitor by ubiquitination of Chk1 [ Pharmacol Res, 2024, 201:107091] | PubMed: 38316371 |
ELK3 destabilization by speckle-type POZ protein suppresses prostate cancer progression and docetaxel resistance [ Cell Death Dis, 2024, 15(4):274] | PubMed: 38632244 |
Loss of POLE3-POLE4 unleashes replicative gap accumulation upon treatment with PARP inhibitors [ Cell Rep, 2024, 43(5):114205] | PubMed: 38753485 |
Crispr-mediated genome editing reveals a preponderance of non-oncogene addictions as targetable vulnerabilities in pleural mesothelioma [ Lung Cancer, 2024, 197:107986] | PubMed: 39383772 |
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8] | PubMed: 36736316 |
Actionable loss of SLF2 drives B-cell lymphomagenesis and impairs the DNA damage response [ EMBO Mol Med, 2023, e16431.] | PubMed: 37485814 |
BRD7 suppresses tumor chemosensitivity to CHK1 inhibitors by inhibiting USP1-mediated deubiquitination of CHK1 [ Cell Death Discov, 2023, 9(1):313] | PubMed: 37626049 |
Selective ATM inhibition augments radiation-induced inflammatory signaling and cancer cell death [ Aging (Albany NY), 2023, 15(2):492-512] | PubMed: 36656721 |
Cyclin A-CDK1 suppresses the expression of the CDK1 activator CDC25A to safeguard timely mitotic entry [ J Biol Chem, 2023, S0021-9258(23)00089-3] | PubMed: 36717077 |
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