YL529, a novel, orally available multikinase inhibitor, potently inhibits angiogenesis and tumour growth in preclinical models.

ABSTRACT:

Background and purpose

Targeted chemotherapy using small-molecule inhibitors of angiogenesis and proliferation is a promising strategy for cancer therapy.

Experimental approach

YL529 was developed via computer-aided drug design, de novo synthesis and high-throughput screening. The biochemical, pharmacodynamic and toxicological profiles of YL529 were investigated using kinase and cell viability assays, a mouse tumour cell-containing alginate bead model, a zebrafish angiogenesis model and several human tumour xenograft models in athymic mice.

Key results

In vitro, YL529 selectively inhibited the activities of VEGFR2/VEGFR3 and serine/threonine kinase RAF kinase. YL529 inhibited VEGF165 -induced phosphorylation of VEGFR2, as well as the proliferation, migration, invasion

SUBMITTER: Xu Y 

PROVIDER: S-EPMC3753834 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature