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

Suliman Almahmoud; Catherine C. Elix; Jeremy O. Jones; Corey R. Hopkins; Jonathan L. Vennerstrom; Haizhen A. Zhong

doi:10.1016/j.bmc.2021.116368

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

Suliman Almahmoud, Catherine C. Elix, Jeremy O. Jones, Corey R. Hopkins, Jonathan L. Vennerstrom, Haizhen A. Zhong

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Article number	116368
Journal	Bioorganic and Medicinal Chemistry
Volume	46
DOIs	https://doi.org/10.1016/j.bmc.2021.116368
State	Published - Sep 15 2021

Keywords

Anticancer
Docking
PPARγ
Prostate cancer
Virtual screening

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2021.116368

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title = "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.",

keywords = "Anticancer, Docking, PPARγ, Prostate cancer, Virtual screening",

author = "Suliman Almahmoud and Elix, {Catherine C.} and Jones, {Jeremy O.} and Hopkins, {Corey R.} and Vennerstrom, {Jonathan L.} and Zhong, {Haizhen A.}",

note = "Funding Information: The authors acknowledge The Saudi Arabian Cultural Mission (SACM) for financial support (to S.A.). In addition, H.A.Z. thanks the Nebraska Research Initiative and College of Arts and Sciences at the University of Nebraska at Omaha for software support. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

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doi = "10.1016/j.bmc.2021.116368",

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AU - Almahmoud, Suliman

AU - Elix, Catherine C.

AU - Jones, Jeremy O.

AU - Hopkins, Corey R.

AU - Vennerstrom, Jonathan L.

AU - Zhong, Haizhen A.

N1 - Funding Information: The authors acknowledge The Saudi Arabian Cultural Mission (SACM) for financial support (to S.A.). In addition, H.A.Z. thanks the Nebraska Research Initiative and College of Arts and Sciences at the University of Nebraska at Omaha for software support. Publisher Copyright: © 2021 Elsevier Ltd

PY - 2021/9/15

Y1 - 2021/9/15

N2 - 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.

AB - 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.

KW - Anticancer

KW - Docking

KW - PPARγ

KW - Prostate cancer

KW - Virtual screening

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

Abstract

Keywords

ASJC Scopus subject areas

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