title: Transporters as drug targets: discovery and development of NPC1L1 inhibitors.
abstract: 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.
authors.affiliation: Section on Lipid Sciences, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Betters
authors.forename: L
authors.initials: L
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001384:Azetidines / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D000069438:Ezetimibe; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009542:Niemann-Pick Diseases / Q000188:drug therapy / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D001384:Azetidines; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D000069438:Ezetimibe