AZD7762 is a potent ATP-competitive checkpoint kinase inhibitor with an IC50 of 5 and <10 nM for CHK1 and CHK2 respectively.AZD7762 has been profiled extensively in vitro andin 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.
|Cell lines||H29 cells|
|Preparation method||Checkpoint Abrogation Assay
HT29 cells (3 × 105) were seeded in 96-well plates and incubated overnight. Cells were treated for 2 h with camptothecin (topoisomerase I inhibitor; 0.07 μg/mL) to induce the G2 checkpoint. Cells were then treated for 20 h with vehicle (0.5% DMSO) or caffeine (4 mmol/L; positive control) plus nocodazole (1 μg/mL) or a 12-point titration of AZD7762 (12.5 μmol/L to 6 nmol/L) plus nocodazole. Nocodazole alone-treated cells with no camptothecin pretreatment were used to determine the maximum mitotic index. Cells were fixed with 3.7% formaldehyde for 1 h, permeabilized with PBS containing 0.05% Triton X, and incubated with anti-phH3 antibody for 1 h followed by Alexa Fluor 488 anti-rabbit (Molecular Probes) and Hoechst stain for 1 h. Mitotic index was determined on the ArrayScan and expressed as the percentage of cells undergoing mitosis. The EC50 was calculated by concentration-response curve fitting using three-variable logistical equations within XLfit (model 205) with the curve bottom constrained to 0 and the top constrained to 100 by nocodazole alone treatment.
|Incubation time||20 h|
|Animal models||athymic mice bearing established H460-DNp53 or SW620 tumors and rnu rats bearing established H460-DNp53 tumors|
|Formulation||formulated in 11.3% hydroxyproplyl-β-cyclodextrin|
|Dosages||25mg/kg(mouse) and 10 or 20mg/kg (rat)|
|Administration||i.v. injection via the tail vein|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Sci Rep. 2017 Nov 14;7(1):15511.
Targeting a non-oncogene addiction to the ATR/CHK1 axis for the treatment of small cell lung cancer
AZD7762 purchased from AbMole
The Chk1 inhibitor AZD7762 sensitises p53 mutant breast cancer cells to radiation in vitro and in vivo.
Ma et al. Mol Med Report. 2012 Oct;6(4):897-903. PMID: 22825736.
The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53-Mutated Multiple Myeloma Cells.
Landau et al. Mol Cancer Ther. 2012 Aug;11(8):1781-8. PMID: 22653969.
Discovery of checkpoint kinase inhibitor (S)-5-(3-fluorophenyl)-N-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by structure-based design and optimization of thiophenecarboxamide ureas.
Oza et al. J Med Chem. 2012 Jun 14;55(11):5130-42. PMID: 22551018.
Potentiation of the novel topoisomerase I inhibitor indenoisoquinoline LMP-400 by the cell checkpoint and Chk1-Chk2 inhibitor AZD7762.
Aris et al. Cancer Res. 2012 Feb 15;72(4):979-89. PMID: 22189968.
AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies.
Zabludoff SD, et al. Mol Cancer Ther. 2008 Sep;7(9):2955-66. PMID: 18790776.
|Related Checkpoint Products|
CCT241533 hydrochloride is a potent serine/threonine checkpoint kinase (Chk2) inhibitor with IC50 of 3 nM.
CCT241533 is a potent serine/threonine checkpoint kinase (Chk2) inhibitor with IC50 of 3 nM.
BML-277 is a high efficient Chk2 inhibitors, IC50 is 15 nM.
AZD7762 hydrochloride is a potent ATP-competitive checkpoint kinase inhibitor with an IC50 of 5 and <10 nM for CHK1 and CHK2 respectively.
CHIR-124 is a novel and potent Chk1 inhibitor with IC50 of 0.3 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.