Discovery of Cytochrome P450 4F11-Activated Inhibitors of Stearoyl Coenzyme A Desaturase

Sarah E. Winterton, Emanuela Capota, Xiaoyu Wang, Hong Chen, Prema L. Mallipeddi, Noelle S. Williams, Bruce A. Posner, Deepak Nijhawan, Joseph M. Ready

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Stearoyl CoA desaturase (SCD) catalyzes the first step in the conversion of saturated fatty acids to unsaturated fatty acids. Unsaturated fatty acids are required for membrane integrity and for cell proliferation. For these reasons, inhibitors of SCD represent potential treatments for cancer. However, systemically active SCD inhibitors result in skin toxicity, which presents an obstacle to their development. We recently described a series of oxalic acid diamides that are converted into active SCD inhibitors within a subset of cancers by CYP4F11-mediated metabolism. Herein we describe the optimization of the oxalic acid diamides and related N-acyl ureas, and an analysis of the structure-activity relationships related to metabolic activation and SCD inhibition.

Original languageEnglish (US)
JournalJournal of Medicinal Chemistry
DOIs
StateAccepted/In press - Jan 12 2018

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Stearoyl-CoA Desaturase
Cytochrome P-450 Enzyme System
Unsaturated Fatty Acids
Structure-Activity Relationship
Urea
Neoplasms
Fatty Acids
Cell Proliferation
stearoyl-coenzyme A
Skin
Membranes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Discovery of Cytochrome P450 4F11-Activated Inhibitors of Stearoyl Coenzyme A Desaturase. / Winterton, Sarah E.; Capota, Emanuela; Wang, Xiaoyu; Chen, Hong; Mallipeddi, Prema L.; Williams, Noelle S.; Posner, Bruce A.; Nijhawan, Deepak; Ready, Joseph M.

In: Journal of Medicinal Chemistry, 12.01.2018.

Research output: Contribution to journalArticle

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AU - Williams, Noelle S.

AU - Posner, Bruce A.

AU - Nijhawan, Deepak

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