Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors.

ABSTRACT:

Background

Activating mutations in Kit receptor tyrosine kinase or the related platelet-derived growth factor receptor (PDGFR) play an important role in the pathogenesis of gastrointestinal stromal tumors (GIST).

Methods

This study investigated the activity of motesanib, an inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3; PDGFR; and Kit, against primary activating Kit mutants and mutants associated with secondary resistance to imatinib. Single- and double-mutant isoforms of Kit were evaluated for their sensitivity to motesanib or imatinib in autophosphorylation assays and in Ba/F3 cell proliferation assays.

Results

Motesanib inhibited Kit autophosphorylation in CHO cell lines expressing primary activating mutations in exon 9 (AYins503-504

SUBMITTER: Caenepeel S 

PROVIDER: S-EPMC2912835 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature