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Products are for research use only. Not for human use. We do not sell to patients.
(AZD7762; AZD 7762)
AZD-7762 Chemical Structure
|Product name: AZD-7762|
|Cat. No.: HY-10992|
AZD7762 is a potent and selective inhibitor of Chk1 with IC50 of 5 nM; equally potent against Chk2 and less potent against CAM, Yes, Fyn, Lyn, Hck and Lck.
IC50 Value: 5 nM
in vitro: AZD-7762 is a novel checkpoint kinase inhibitor with an IC50 of 5 and <10 nM for CHK1 and CHK2, respectively. 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 gemcitabine against SW620 and topotecan 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. 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.
in vivo: AZD-7762 significantly prolonged the median time required for tumor volume doubling in response to gemcitabine and radiation. 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 with gemcitabine (60 mg/kg), 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 with gemcitabine (10 mg/kg) 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 with irinotecan (25 or 50 mg/kg) causes complete tumor regression in the SW620 xenograft mice with the %T/C increasing significantly to -66% and -67%, respectively.
|M.Wt||362.42||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
DMSO ≥70mg/mL Water <1.2mg/mL Ethanol ≥2.6mg/mL
|1 mg||5 mg||10 mg|
|1 mM||2.7592 mL||13.7961 mL||27.5923 mL|
|5 mM||0.5518 mL||2.7592 mL||5.5185 mL|
|10 mM||0.2759 mL||1.3796 mL||2.7592 mL|
. 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 Jun 15;70(12):4972-81.
. Landau HJ, McNeely SC, Nair JS, Comenzo RL, Asai T, Friedman H, Jhanwar SC, Nimer SD, Schwartz GK.The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53-Mutated Multiple Myeloma Cells.Mol Cancer Ther. 2012 Aug;11(8):1781-8. Epub 2012 May 31.
. Oza V, Ashwell S, Almeida L, Brassil P, Breed J, Deng C, Gero T, Grondine M, Horn C, Ioannidis S, Liu D, Lyne P, Newcombe N, Pass M, Read J, Ready S, Rowsell S, Su M, Toader D, Vasbinder M, Yu D, Yu Y, Xue Y, Zabludoff S, Janetka J.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.J Med Chem. 2012 Jun 14;55(11):5130-42. Epub 2012 Jun 4.
. Aris SM, Pommier Y.Potentiation of the novel topoisomerase I inhibitor indenoisoquinoline LMP-400 by the cell checkpoint and Chk1-Chk2 inhibitor AZD7762.Cancer Res. 2012 Feb 15;72(4):979-89. Epub 2011 Dec 21.
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