Small Molecule Chemistry | Cell Growth & Division | Cytoskeleton | Drug Discovery & Design | Cancer Therapeutics | Toxicology
Targeting the anaphase promoting complex/cyclosome to inhibit cell cycle and to induce apoptosis
J Christopher States*, Cory A France, B Frazier Taylor, John O Trent
*Corresponding author: J Christopher States
Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA
Center for Genetics and Molecular Medicine, University of Louisville, Louisville, KY, USA
Brown Cancer Center, University of Louisville, Louisville, KY, USA
F1000Posters 2012, 3: 258 (poster) [English]
Society of Toxicology Annual Meeting & ToxExpo 2012, 11 - 15 Mar 2012, 2049
Most drugs that cause mitotic arrest disrupt microtubule function by interfering with tubulin polymerization or depolymerization. Resistance to these drugs is a major problem in cancer chemotherapy. The purpose of this research is to develop new drugs to induce mitotic arrest and apoptosis by targeting the master regulator of mitosis (anaphase promoting complex) rather than tubulin.
We developed homology structure models for anaphase promoting complex subunits 2 and 11, and then used these for in silico docking experiments to identify candidate compounds to interfere with the anaphase promoting complex assembly. Preliminary testing identified two lead compounds that induce the expected phenotype in treated cells.
To further characterize the system showing mechanism(s) of action, and demonstrate binding of lead candidates to the target protein in vitro.
US Provisional Patent 61/479,939 filed 4/28/2011.
National Institutes of Health (NIH), T35ES014559
National Institutes of Health (NIH), F30ES013372
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