Enhanced Properties of a Benzimidazole Benzylpyrazole Lysine Demethylase Inhibitor: Mechanism-of-Action, Binding Site Analysis, and Activity in Cellular Models of Prostate Cancer
David M. Carter, Edgar Specker, P.H. Malecki, Jessica Przygodda, Krystyna Dudaniec, M.S. Weiss, Udo Heinemann, Marc Nazaré, U. Gohlke
Abstract
and by populating a distal site on the enzyme surface. Furthermore, we provide evidence that the inhibitor's cytostatic properties arise from direct intracellular inhibition of KDM4 enzymes. PCa cells treated with the inhibitor exhibit reduced expression of genes regulated by the androgen receptor, an outcome accompanied by epigenetic maintenance of a heterochromatic state.
Topics & Concepts
ChemistryDemethylaseEnzymeBiochemistryMechanism of actionBenzimidazoleBinding siteEpigeneticsGeneIn vitroOrganic chemistryEpigenetics and DNA MethylationProstate Cancer Treatment and ResearchHistone Deacetylase Inhibitors Research