Cat. No. Name Size Price Add Cart
KI0184AZD77622 mg$112
AZD77625 mg$192
AZD776225 mg$592
AZD7762100 mg$1552

Chemical Characteristic

Product NameAZD7762
CAS No.860352-01-8
Molecular Weight 362.42
FormulaC17H19FN4O2S
Chemical Name1-(2-((S)-piperidin-3-ylcarbamoyl)-5-(3-fluorophenyl)thiophen-3-yl)urea
SmilesN(C(=O)N)c1c(sc(c1)c1cc(ccc1)F)C(=O)NC1CNCCC1
Chemical Structure
DocumentsHPLC MS

Biological activities

AZD7762 is a novel ATP-competitive and selective checkpoint kinase inhibitor with IC50 values of 5 and < 10 nM for checkpoint kinases 1 (CHK1) and checkpoint kinases 2 (CHK2), respectively. AZD7762 abrogates the G2 arrest induced by camptothecin with an average EC50 value of 10 nM and maximal abrogation in the range of 100 nM. AZD7762 alone induces cell arrest with an EC50 value of 620 nM. AZD7762 (100 nM) enhances cytotoxicity in p53-mutant tumor cell lines.[1] AZD7762 significantly sensitizes MiaPaCa-2 cells to radiation, producing a radiation enhancement ratio (RER) of 1.5. The combination of AZD7762 with gemcitabine further enhances radiosensitization with RER of 1.9. In MPanc96 cells, AZD7762 produces sensitization to radiation with RER of 1.4. The combination of AZD7762 with gemcitabine enhances radiosensitization with RER of 1.5.[2] AZD7762 (100 nM) abrogates the S-phase arrest induced by LMP-400 or CPT in HT29 cells. AZD7762 also blocks LMP-400??nduced autophosphorylations of both CHK1 and CHK2.[3] In the mouse H460-DNp53 xenograft model, AZD7762 (25 mg/kg) significantly potentiates gemcitabine in the combination group resulting in a log cell kill of 0.9 or percent treated/control (%T/C) of 26, although AZD7762 alone doesn?? show significant antitumor activity. AZD7762 and gemcitabine combination group has a slight but not statistically significant body weight loss (7%) compared with the gemcitabine alone control group (no loss). In the mouse SW620 xenograft model, AZD7762 (25 mg/kg) in combination with gemcitabine shows significant antitumor activity compared with AZD7762 alone. Irinotecan with increasing dose (25 mg/kg and 50 mg/kg) in combination with AZD7762 (25 mg/kg), % T/C increases significantly from 9 and 1 to -66% and -67%, respectively. Furthermore, in the rat H460-DNp53 xenograft model, AZD7762 potentiates the antitumor activity of gemcitabine in a dose-dependent manner, by a decrease in %T/C with increasing dose (48% and 32%, 10 and 20 mg/kg AZD7762, respectively).[1] In pancreatic MiaPaCa-2 xenografts model, AZD7762 (20 mg/kg) alone produces a significant growth delay (δ = 3 days compared with control). The combinations of AZD7762 with gemcitabine or gemcitabine-radiation significantly prolongs the time required for tumor volume doubling relative to gemcitabine alone (δ = 8 days) or gemcitabine-radiation (δ >35 days). Furthermore, AZD7762 (20 mg/kg) inhibits S296 CHK1 in the presence of gemcitabine, radiation, and gemcitabine-radiation in tumors.[2]

Protocols

AZD7762 is prepared as dimethyl sulfoxide (DMSO) stocks at 10 mM. [3]

References

[1] Zabludoff SD, et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther. 2008, 7(9): 2955-2966.
[2] Morgan MA, et al. Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Res. 2010, 70(12): 4972-4981.
[3] Aris SM, et al. Potentiation of the novel topoisomerase I inhibitor indenoisoquinoline LMP-400 by the cell checkpoint and Chk1-Chk2 inhibitor AZD7762. Cancer Res. 2012, 72(4): 979-989.

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