Back to products

Browse products

Approved anticancer agents

Anticancer agents in trials

Anticancer agents in preclinical trials

Anticancer molecular libraries

MedKoo product information:

AZD-7762

AZD-7762 is a synthetic small molecule inhibitor of checkpoint kinases (Chks) with potential chemosensitizing activity. AZD7762 binds to and inhibits Chks, which may prevent cell cycle arrest and subsequent nucleotide excision repair in DNA-damaged tumor cells, resulting in tumor cell apoptosis. This agent may enhance the cytotoxicity of DNA-damaging agents. Chks are protein kinases that regulate either G1/S or G2/M transitions in the cell cycle. In the presence of DNA damage or incomplete DNA replication, Chks become activated and initiate cell cycle arrest to allow DNA repair or the completion of DNA replication. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Current developer:   AstraZeneca.

AZD7762, a potent ATP-competitive checkpoint kinase inhibitor in clinical trials. AZD7762 has been profiled extensively in vitro and in vivo in combination with DNA-damaging agents and has been shown to potentiate response in several different settings where inhibition of checkpoint kinase results in the abrogation of DNA damage-induced cell cycle arrest. Dose-dependent potentiation of antitumor activity, when AZD7762 is administered in combination with DNA-damaging agents, has been observed in multiple xenograft models with several DNA-damaging agents, further supporting the potential of checkpoint kinase inhibitors to enhance the efficacy of both conventional chemotherapy and radiotherapy and increase patient response rates in a variety of settings. (source: Mol Cancer Ther. 2008 Sep;7(9):2955-66.).

1: Mitchell JB, Choudhuri R, Fabre K, Sowers AL, Citrin D, Zabludoff SD, Cook JA. In vitro and in vivo radiation sensitization of human tumor cells by a novel checkpoint kinase inhibitor, AZD7762. Clin Cancer Res. 2010 Apr 1;16(7):2076-84. Epub 2010 Mar 16. PubMed PMID: 20233881; PubMed Central PMCID: PMC2851146.

2: McNeely S, Conti C, Sheikh T, Patel H, Zabludoff S, Pommier Y, Schwartz G, Tse A. Chk1 inhibition after replicative stress activates a double strand break response mediated by ATM and DNA-dependent protein kinase. Cell Cycle. 2010 Mar;9(5):995-1004. Epub 2010 Mar 14. PubMed PMID: 20160494.

3: Goteti K, Garner CE, Utley L, Dai J, Ashwell S, Moustakas DT, Gönen M, Schwartz GK, Kern SE, Zabludoff S, Brassil PJ. Preclinical pharmacokinetic/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents. Cancer Chemother Pharmacol. 2010 Jul;66(2):245-54. Epub 2009 Oct 16. PubMed PMID: 19841922.

4: Wagner JM, Karnitz LM. Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival. Mol Pharmacol. 2009 Jul;76(1):208-14. Epub 2009 Apr 29. PubMed PMID: 19403702; PubMed Central PMCID: PMC2701464.

5: Zabludoff SD, Deng C, Grondine MR, Sheehy AM, Ashwell S, Caleb BL, Green S, Haye HR, Horn CL, Janetka JW, Liu D, Mouchet E, Ready S, Rosenthal JL, Queva C, Schwartz GK, Taylor KJ, Tse AN, Walker GE, White AM. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther. 2008 Sep;7(9):2955-66. PubMed PMID: 18790776.

6: Ashwell S, Janetka JW, Zabludoff S. Keeping checkpoint kinases in line: new selective inhibitors in clinical trials. Expert Opin Investig Drugs. 2008 Sep;17(9):1331-40. Review. PubMed PMID: 18694366.