AZD-7762 hydrochloride 

AZD-7762 hydrochloride is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with an IC₅₀ of 5 nM for Chk1.

AZD-7762 hydrochloride (AZD7762) is an equally potent inhibitor of Chk1 and Chk2 in vitro. AZD-7762 hydrochloride potently inhibits Chk1 and Chk2, abrogates DNA damage-induced S and G₂ checkpoints, enhances the efficacy of NSC 613327 and SKF 104864A, and modulates downstream checkpoint pathway proteins. AZD-7762 hydrochloride potently inhibits Chk1 phosphorylation of a cdc25C peptide with an IC₅₀ of 5 nM as measured by a scintillation proximity assay. The K_i for AZD-7762 hydrochloride is determined to be 3.6 nM. Kinetic characterization suggests that AZD-7762 hydrochloride binds in the ATP-binding site of Chk1 and is thought to compete directly for ATP binding in a reversible manner. AZD-7762 hydrochloride is shown to abrogate the G₂ arrest induced by Camptothecin with an average EC₅₀ of 10 nM (n=12) and maximal abrogation in the range of 100 nM^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In rat H460-DNp53 xenograft studies, AZD-7762 hydrochloride (10 mg/kg and 20 mg/kg) potentiates the antitumor activity of NSC 613327 in a dose-dependent manner. That is, the inhibition rate (%T/C) decreases to 48% and 32%, respectively, with increasing dose. In a mouse xenograft study in combination with CPT-11, treatment with AZD-7762 hydrochloride in combination with CPT-11 significantly increased CPT-11 activity with a significant increase in %T/C to -66% and -67%, respectively^[1]. AZD7762 hydrochloride in combination with CX-5461 induces Tp53-null (Tp53^-/-) Eμ-Myc in vitro and in vivo Lymphoma cell death^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

398.88

C₁₇H₂₀ClFN₄O₂S

1246094-78-9

O=C(C1=C(NC(N)=O)C=C(C2=CC=CC(F)=C2)S1)N[C@@H]3CNCCC3.Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Zabludoff SD, et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther. 2008 Sep;7(9):2955-66.  [Content Brief]

  [2]. Quin J, et al. Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling. Oncotarget. 2016 Aug 2;7(31):49800-49818.  [Content Brief]