Small Molecule Inhibitors Targeting Biosynthesis of Ceramide, the Central Hub of the Sphingolipid Network

Research output: Contribution to journalReview articlepeer-review

Abstract

Ceramides are composed of a sphingosine and a single fatty acid connected by an amide linkage. As one of the major classes of biologically active lipids, ceramides and their upstream and downstream metabolites have been implicated in several pathological conditions including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation. Consequently, tremendous efforts have been devoted to deciphering the dynamics of metabolic pathways involved in ceramide biosynthesis. Given that several distinct enzymes can produce ceramide, different enzyme targets have been pursued depending on the underlying disease mechanism. The main objective of this review is to provide a comprehensive overview of small molecule inhibitors reported to date for each of these ceramide-producing enzymes from a medicinal chemistry perspective.

Original languageEnglish (US)
Pages (from-to)279-297
Number of pages19
JournalJournal of medicinal chemistry
Volume64
Issue number1
DOIs
StatePublished - Jan 14 2021

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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