Published in

American Chemical Society, Journal of Medicinal Chemistry, 9(58), p. 3757-3766, 2015

DOI: 10.1021/jm5019252

Links

Tools

Export citation

Search in Google Scholar

New Inhibitors of Angiogenesis with Antitumor Activity in Vivo

This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
  • Must obtain written permission from Editor
  • Must not violate ACS ethical Guidelines
Orange circle
Postprint: archiving restricted
  • Must obtain written permission from Editor
  • Must not violate ACS ethical Guidelines
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

Angiogenesis is a requirement for the sustainable growth and proliferation of solid tumors and the development of new compounds that induce a sustained inhibition of the pro-angiogenic signaling generated by tumor hypoxia still remains as an important unmet need. In this work we describe a new anti-angiogenic compound (22) which inhibits the pro-angiogenic signaling under hypoxic conditions in breast cancer cells. Besides, compound 22 blocks the MAPK pathway, impairs cellular migration under hypoxic conditions and regulates a set of genes related with angiogenesis. These responses are mediated by HIF-1α, since when its expression is knocked-down the effects of compound 22 mostly disappear. Furthermore, administration of compound 22 in a xenograft model of breast cancer produced tumor growth reductions ranging from 46% to 55% in 38% of the treated animals without causing any toxic side effect. Importantly, in the responding tumors, a significant reduction in the number of blood vessels was observed, further supporting the mechanism of action of the compound. These findings provide a rationale for the development of new antiangiogenic compounds that could eventually lead to new drugs suitable for the treatment of some types of tumors alone or in combination with other agents.