Virtual screening and biological evaluation of PPARγ antagonists as potential anti-prostate cancer agents.

Abstract

The peroxisome proliferator-activated receptor gamma (PPARγ) was identified as an oncogene and it plays a key role in prostate cancer (PC) development and progression. PPARγ antagonists have been shown to inhibit PC cell growth. Herein, we describe a virtual screening-based approach that led to the discovery of novel PPARγ antagonist chemotypes that bind at the allosteric pocket. Arg288, Lys367, and His449 appear to be important for PPARγ antagonist binding.

• Authors: Suliman Almahmoud, Catherine C Elix, Jeremy O Jones, Corey R Hopkins, Jonathan L Vennerstrom, Haizhen A Zhong
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 46 Pg. 116368 (09 15 2021) ISSN: 1464-3391 [Electronic] England
• PMID: 34433102 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• PPAR gamma

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Drug Screening Assays, Antitumor
• Humans
• Male
• Molecular Structure
• PPAR gamma (antagonists & inhibitors, metabolism)
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Structure-Activity Relationship
• Tumor Cells, Cultured