Reference Detail

Ref Type

Journal Article

PMID

(21531814)

Authors

Wong TW, Lee FY, Emanuel S, Fairchild C, Fargnoli J, Fink B, Gavai A, Hammell A, Henley B, Hilt C, Hunt JT, Krishnan B, Kukral D, Lewin A, Malone H, Norris D, Oppenheimer S, Vite G, Yu C

Title

Antitumor and antiangiogenic activities of BMS-690514, an inhibitor of human EGF and VEGF receptor kinase families.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	17	12	2011 Jun 15	4031-41	Clin Cancer Res

URL

Abstract Text

The extensive involvement of the HER kinases in epithelial cancer suggests that kinase inhibitors targeting this receptor family have the potential for broad spectrum antitumor activity. BMS-690514 potently inhibits all three HER kinases, and the VEGF receptor kinases. This report summarizes data from biochemical and cellular pharmacology studies, as well as antitumor activity of BMS-690514.The potency and selectivity of BMS-690514 was evaluated by using an extensive array of enzymatic and binding assays, as well as cellular assays that measure proliferation and receptor signaling. Antitumor activity was evaluated by using multiple xenograft models that depend on HER kinase signaling. The antiangiogenic properties of BMS-690514 were assessed in a matrigel plug assay, and effect on tumor blood flow was measured by dynamic contrast-enhanced MRI.BMS-690514 is a potent and selective inhibitor of epidermal growth factor receptor (EGFR), HER2, and HER4, as well as the VEGF receptor kinases. It inhibits proliferation of tumor cells with potency that correlates with inhibition of receptor signaling, and induces apoptosis in lung tumor cells that have an activating mutation in EGFR. Antitumor activity was observed with BMS-690514 at multiple doses that are well tolerated in mice. There was evidence of suppression of tumor angiogenesis and endothelial function by BMS-690514, which may contribute to its efficacy.By combining inhibition of two receptor kinase families, BMS-690524 is a novel targeted agent that disrupts signaling in the tumor and its vasculature.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
BMS-690514	BMS-690514	0	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
BMS-690514		BMS 690514\|BMS690514	EGFR Inhibitor (Pan) 61 HER2 Inhibitor 41 VEGFR Inhibitor (Pan) 36	BMS-690514 is a pan-EGFR/VEGFR inhibitor, which may result in increased tumor cell apoptosis, and decreased tumor cell proliferation and angiogenesis (PMID: 21531814, PMID: 17616683, PMID: 23490650, PMID: 23468081).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References