Mechanism of action: Epidermal growth factor receptor (EGFR) family (pan-erbB) tyrosine kinase inhibitor

Preclinical pharmacology

AZD8931 is a potent, selective, ATP competitive inhibitor of EGFR and erbB2 (enzyme IC50 of 12 and 14nM, respectively). It inhibited EGFR and erbB2 auto-phosphorylation in cellular assays with IC50 values of 2 and 59nM, respectively. Compared to selective EGFR (gefitinib) or erbB2 inhibitors, AZD8931 was a much more potent inhibitor of EGF-driven cellular proliferation in multiple tumour cell lines.

Treatment of mice and rats bearing a variety of xenografted tumours, including breast, lung, gastric and prostate carcinomas, with AZD8931 resulted in dose-dependent inhibition of tumour growth at well tolerated doses, and produced regressions in some models. Anti-tumour effects were accompanied by pharmacodynamic inhibition of the relevant targets; that is, AZD8931 administered orally for four days at 50mg/kg (105μmol/kg) completely inhibited EGFR phosphorylation in LoVo xenografts and at 40mg/kg (85μmol/kg) inhibited erbB2 phosphorylation by 69% in erbB2-SW620 xenografts. Furthermore, AZD8931 at 50 and 25mg/kg (105 and 53μmol/kg) produced dose-dependent inhibition of EGFR (88% and 67%) and erbB2 (90% and 59%) phosphorylation in BT474C tumour xenografts.

AZD8931 at 50mg/kg (105μmol/kg) completely inhibited rat ovulation, an EGFR-regulated physiological process.

Additional Information

Clinical Trials for this compound

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Publications for this compound

Find out more about this compound by reading related Publications:

Clinical Cancer Research

AZD8931, an Equipotent, Reversible Inhibitor of Signaling by Epidermal Growth Factor Receptor, ERBB2 (HER2), and ERBB3: A Unique Agent for Simultaneous ERBB Receptor Blockade in Cancer

ACS Medicinal Chemistry Letters

Discovery of AZD8931, an Equipotent, Reversible Inhibitor of Signaling by EGFR, HER2, and HER3 Receptors

Gene information from the NCBi

This compound works on the following genes: