Proto-oncogene serine/threonine-protein kinase PIM-1 is one of the potential therapeutic targets for prostate cancer because it acts as oncoprotein and is involved in prostate tumorigenesis. The search for PIM1 kinase inhibitors is reported and the inhibitors are in various stages of drug development. Our effort in the identification of potent PIM1 kinase inhibitors through ligand based virtual screening allowed us to the identification of few potential hits and the results were reported. In a continuous effort, we utilized another well-known effective <i>In silico</i> structure based virtual high throughput screening method in which we screened 4,591,276 lead-like compounds from zinc database. Lead like compounds were downloaded from zinc database and OMEGA, an openeye tool was used to generate multiple conformations. Receptor grid file was generated by taking X-ray crystal structure of pim-1 kinase- bound with inhibitor (3R04). Docking Program, FRED was employed to dock the compounds and the resulted hits were prioritized based on their binding mode and Chemgauss score. We purchased 25 compounds form Enamine and Chembridge screening libraries. The PIM1 inhibitory activity using CycLex PIM1 kinase assay was determined for all the purchased compounds. Among the 25 structure-based screening hits tested, three compounds 4, 13 and 22 were selected based on their inhibitory activity and optimization of the hits to lead will pave the way for a new class of drugs for the treatment of prostate cancer.

Identification of PIM1 kinase inhibitors by structure-based virtual high throughput screening

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.