AZD-7762

• CAT Number: I005163
• CAS Number: 860352-01-8
• Molecular Formula: C₁₇H₁₉FN₄O₂S
• Molecular Weight: 362.42
• Purity: ≥95%
• Synonyms: AZD-7762; AZD7762; 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide
• Target: Checkpoint Kinase (Chk)
• Solubility: DMSO ≥70mg/mL Water <1.2mg/mL Ethanol ≥2.6mg/mL
• Storage: -20°C
• IC50: 5 nM
• IUPAC Name: 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide
• InChI: 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
• InChIKey: IAYGCINLNONXHY-LBPRGKRZSA-N
• SMILES: C1C[C@@H](CNC1)NC(=O)C2=C(C=C(S2)C3=CC(=CC=C3)F)NC(=O)N

AZD-7762（Cat No.:I005163）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.

Overview of Clinical Research

Originator: AstraZeneca
Class: Antineoplastics
Mechanism of Action: Checkpoint kinase 1 inhibitors; Checkpoint kinase 2 inhibitors
Orphan Drug Status: No
New Molecular Entity: Yes

Reference

1:J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Feb 15;1044-1045:70-76. doi: 10.1016/j.jchromb.2016.12.031. Epub 2016 Dec 30. HPLC-UV method for simultaneous determination of MK-1775 and AZD-7762 in both acetonitrile-aqueous solution and mouse plasma.Ebeid K,Ho GN,Salem AK, PMID: 28088043 PMCID: PMC5296315 [Available on 2018-02-15] DOI: 10.1016/j.jchromb.2016.12.031
Abstract: A sensitive and precise method is described for the simultaneous determination of two small molecule kinase inhibitors: MK-1775 (MK) and AZD-7762 (AZD), in acetonitrile (ACN)-aqueous solution and in mouse plasma. A Nova-Pak C18 reversed phase column (3.9mm×150mm, 4μm, 60Å) was utilized in the separation using an isocratic mobile phase of 0.1% v/v triethylamine in phosphate buffer (pH=7.4): acetonitrile (ACN) (60:40, v/v), at a flow rate of 0.8mL/min. Detection wavelength was set at 310nm for both MK and AZD, and 431nm for the internal standard sunitinib (SUN). The developed method was validated following the ICH guidelines and it was shown to be accurate, precise and linear in the range of 41ng/mL to 8333ng/mL for both drugs in the ACN-aqueous solution and from 83ng/mL to 8333ng/mL for both drugs in mouse plasma samples. For the first time, the presented data suggest the suitability of this method for the simultaneous separation and quantification of MK and AZD in both ACN aqueous solution as well as in mouse plasma samples.Copyright © 2016 Elsevier B.V. All rights reserved.