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转运蛋白作为药物靶点：NPC1L1 抑制剂的发现和开发。

Transporters as drug targets: discovery and development of NPC1L1 inhibitors.

机构信息

Section on Lipid Sciences, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

出版信息

Clin Pharmacol Ther. 2010 Jan;87(1):117-21. doi: 10.1038/clpt.2009.209. Epub 2009 Nov 11.

DOI:10.1038/clpt.2009.209
PMID:19907422
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.

摘要

强效胆固醇吸收抑制剂依折麦布在其分子靶点 NPC1L1 被鉴定之前，就被开发为治疗高胆固醇血症的首创药物。NPC1L1 蛋白介导固醇在肠上皮细胞刷状缘膜中的转运，是肠道胆固醇吸收所必需的，而胆固醇吸收是控制全身胆固醇动态平衡的主要途径。阐明 NPC1L1 依赖性胆固醇吸收的机制将极大地促进治疗高胆固醇血症和其他与胆固醇相关的代谢紊乱的新型降胆固醇药物的发现和开发。

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Transporters as drug targets: discovery and development of NPC1L1 inhibitors.转运蛋白作为药物靶点：NPC1L1 抑制剂的发现和开发。
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2
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