High content screening of diverse compound libraries identifies potent modulators of tubulin dynamics.

ABSTRACT: Tubulin modulating agents such as the taxanes are among the most effective antimitotic cancer drugs, although resistance and toxicity present significant problems in their clinical use. However, most tubulin modulators are derived from complex natural products, which can make modification of their structure to address these problems difficult. Here, we report the discovery of new antimitotic compounds with simple structures that can be rapidly synthesized, through the phenotypic screening of a diverse compound library for the induction of mitotic arrest. We first identified a compound, which induced mitotic arrest in human cells at submicromolar concentrations. Its simple structure enabled rapid exploration of activity, defining a biphenylacetamide moiety required for activity, A family of

SUBMITTER: Laraia L 

PROVIDER: S-EPMC4027768 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature