title: 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.
authors.affiliation: Department of Chemistry.
authors.forename: Eugene L Piatnitski
authors.initials: EL
authors.lastname: Chekler
authors.affiliation: Department of Chemistry.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Kiselyov
authors.affiliation: Department of Chemistry.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Ouyang
authors.affiliation: Department of Chemistry.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Chemistry.
authors.forename: Vatee
authors.initials: V
authors.lastname: Pattaropong
authors.affiliation: Department of Cell Biology.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell Biology.
authors.forename: M Carolina
authors.initials: MC
authors.lastname: Tuma
authors.affiliation: Department of Cell Biology.
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Doody
keywords: Tubulin; VEGFR; angiogenesis; antimitotic; tumor vasculature; vascular disrupting agent