Small Molecule Inhibitors Targeting Biosynthesis of Ceramide, the Central Hub of the Sphingolipid Network
- 4 January 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 64 (1), 279-297
- https://doi.org/10.1021/acs.jmedchem.0c01664
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.Keywords
Funding Information
- Alzheimer's Association (T-PEP-18-579974C)
- Rainwater Charitable Foundation (T-PEP-18-579974C)
- National Institute on Aging (R01AG059799)
- National Institute of Mental Health (P30MH075673)
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University
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