WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200311
CAS#: 860352-01-8 (free base)
Description: 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.
MedKoo Cat#: 200311
CAS#: 860352-01-8 (free base)
Chemical Formula: C17H19FN4O2S
Exact Mass: 362.12127
Molecular Weight: 362.42
Elemental Analysis: C, 56.34; H, 5.28; F, 5.24; N, 15.46; O, 8.83; S, 8.85
Synonym: AZD7762; AZD 7762; AZD-7762.
IUPAC/Chemical Name: (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide
InChi Key: IAYGCINLNONXHY-LBPRGKRZSA-N
InChi Code: InChI=1S/C17H19FN4O2S/c18-11-4-1-3-10(7-11)14-8-13(22-17(19)24)15(25-14)16(23)21-12-5-2-6-20-9-12/h1,3-4,7-8,12,20H,2,5-6,9H2,(H,21,23)(H3,19,22,24)/t12-/m0/s1
SMILES Code: O=C(C1=C(NC(N)=O)C=C(C2=CC=CC(F)=C2)S1)N[C@@H]3CNCCC3
Appearance: white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 362.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
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, GÃ¶nen 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.
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.).
(source: Mol Cancer Ther. 2008 Sep;7(9):2955-66.).