A Short Review on Obeticholic Acid: An Effective Modulator of Farnesoid X Receptor

IF 1.3 Q4 PHARMACOLOGY & PHARMACY

Current Reviews in Clinical and Experimental Pharmacology Pub Date : 2023-10-05 DOI:10.2174/0127724328239536230919070001

Anila Kutty Narayanan, Sudhindran Surendran, Dinesh Balakrishnan, Unnikrishnan Gopalakrishnan, Shweta Malick, Arun Valsan, Abby Cyriac Philips, Christopher J Watson

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Abstract

Abstract: Farnesoid X receptor (FXR) was identified as an orphan nuclear receptor resembling the steroid receptor in the late ’90s. Activation of FXR is a crucial step in many physiological functions of the liver. A vital role of FXR is impacting the amount of bile acids in the hepatocytes, which it performs by reducing bile acid synthesis, stimulating the bile salt export pump, and inhibiting its enterohepatic circulation, thus protecting the hepatocytes against the toxic accumulation of bile acids. Furthermore, FXR mediates bile acid biotransformation in the intestine, liver regeneration, glucose hemostasis, and lipid metabolism. In this review, we first discuss the mechanisms of the disparate pleiotropic actions of FXR agonists. We then delve into the pharmacokinetics of Obeticholic acid (OCA), the first-in-class selective, potent FXR agonist. We additionally discuss the clinical journey of OCA in humans, its current evidence in various human diseases, and its plausible roles in the future.

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奥贝胆酸:一种有效的法内甾体X受体调节剂

摘要:Farnesoid X受体(FXR)是上世纪90年代末发现的一种类似类固醇受体的孤儿核受体。FXR的激活是肝脏许多生理功能的关键步骤。FXR的一个重要作用是影响肝细胞中胆汁酸的数量，它通过减少胆汁酸合成，刺激胆盐输出泵，抑制其肠肝循环，从而保护肝细胞免受胆汁酸的毒性积累。此外，FXR介导胆汁酸在肠道的生物转化、肝脏再生、葡萄糖止血和脂质代谢。在这篇综述中，我们首先讨论了FXR激动剂不同的多效性作用的机制。然后，我们深入研究了奥贝胆酸(OCA)的药代动力学，这是一种一流的选择性强效FXR激动剂。我们还讨论了OCA在人类中的临床历程，它目前在各种人类疾病中的证据，以及它在未来的可能作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Reviews in Clinical and Experimental Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

4.80

自引率

9.10%

发文量