Friday, October 2, 2015

Drugs in Clinical Pipeline: AZD2932

AZD2932 [2-(4-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)-N-(1-isopropyl-1H-pyrazol-4-yl)acetamide] is a potent and mutil-targeted protein tyrosine kinase inhibitor with IC50 of 8 nM, 4 nM, 7 nM, and 9 nM for VEGFR-2, PDGFR-β, Flt-3, and c-Kit, respectively [1].

AZD2932 does not inhibit the various cytochrome P450 isoforms with the worst IC50 being against 2C9 (IC50 = 8.0 uM). It has a good fraction unbound between 3.3% free in human and 7.0% in dog sera and has no activity against hERG (IC50 = 137 uM).

AZD2932 belong to the quinazoline family of kinase inhibitors, where fine-tuning of the lipophilicity of the pyrazole series provided a balanced 1:1 ratio of activity vs both VEGFR-2 and PDGFR-β. Moreover, AZD2932 potently inhibited both PDGFR-α (IC50 = 2 nM) and PDGFR-β (IC50 = 4 nM) phosphorylation with a correlation close to 1:1.

Common Name: AZD2932
Synonyms: AZD2932; AZD 2932; AZD-2932
IUPAC Name: 2-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)phenyl)-N-(1-isopropyl-1H-pyrazol-4-yl)acetamide
CAS Number: 883986-34-3
Mechanism of Action: Kinase Inhibitor; Multi-Kinase Inhibitor; KDR Inhibitor;  PDGFR Inhibitor; Angiogenesis Inhibitor
Indication: Various Cancers; Anti-tumor Therapy
Development Stage: Pre-Clinical

Company: AstraZeneca

1. Ple, P. A.; et. al. Discovery of AZD2932, a new Quinazoline Ether Inhibitor with high affinity for VEGFR-2 and PDGFR tyrosine kinases. Bioorg Med Chem Lett 2012, 22(1), 262-266.