Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors.

ABSTRACT:

Background

Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor receptor (VEGFR) often inhibit other kinases, which may contribute to their adverse-event profiles.

Methods

Kinase selectivity of pazopanib, sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular potency was measured using autophosphorylation assays. Effect on human bone marrow progenitor growth in the presence of multiple growth factors was evaluated and correlated with the kinase selectivity.

Results

Sunitinib inhibited more kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All th

SUBMITTER: Kumar R 

PROVIDER: S-EPMC2768111 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature