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Discovery of Dual VEGFR-2 and Tubulin Inhibitors with in Vivo Efficacy.

ABSTRACT: In an effort to develop potent, orally bioavailable compounds for the treatment of neoplastic diseases, we developed a class of dual VEGFR-2 kinase and tubulin inhibitors. Targeting the VEGFR receptor kinase and tubulin structure allows for inhibition of both tumor cells and tumor vasculature. Previously, a combination of two compounds, a VEGF receptor tyrosine kinase inhibitor and tubulin agent, was demonstrated to produce an enhanced antitumor response in animal studies. We have reaffirmed their results, with the added benefit that both activities are found in one compound.

SUBMITTER: Chekler EL

PROVIDER: S-EPMC4007844 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Discovery of Dual VEGFR-2 and Tubulin Inhibitors with in Vivo Efficacy.

Chekler Eugene L Piatnitski EL Kiselyov Alexander S AS Ouyang Xiaohu X Chen Xiaoling X Pattaropong Vatee V Wang Ying Y Tuma M Carolina MC Doody Jacqueline F JF

ACS medicinal chemistry letters 20100820 9

In an effort to develop potent, orally bioavailable compounds for the treatment of neoplastic diseases, we developed a class of dual VEGFR-2 kinase and tubulin inhibitors. Targeting the VEGFR receptor kinase and tubulin structure allows for inhibition of both tumor cells and tumor vasculature. Previously, a combination of two compounds, a VEGF receptor tyrosine kinase inhibitor and tubulin agent, was demonstrated to produce an enhanced antitumor response in animal studies. We have reaffirmed the ...[more]

PMID: 24900236

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