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Transporters as Drug Targets: Discovery and Development of NPC1L1 Inhibitors
Author(s) -
Betters J L,
Yu L
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.209
Subject(s) - drug discovery , drug development , transporter , drug , pharmacology , chemistry , computational biology , biology , biochemistry , gene
The potent cholesterol absorption inhibitor ezetimibe was developed as a first‐in‐class drug for treating hypercholesterolemia even before its molecular target, Niemann–Pick C1‐like 1 (NPC1L1), had been identified. The NPC1L1 protein mediates sterol transport across the enterocyte brush border membrane and is essential for intestinal cholesterol absorption, a major pathway controlling whole‐body cholesterol homeostasis. An elucidation of the mechanism underlying NPC1L1‐dependent cholesterol absorption would greatly facilitate the discovery and development of new cholesterol‐lowering agents for treating hypercholesterolemia and other cholesterol‐related metabolic disorders. Clinical Pharmacology & Therapeutics (2010) 87 1, 117–121. doi: 10.1038/clpt.2009.209