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JOURNAL ARTICLE
REVIEW
FXR modulators for enterohepatic and metabolic diseases.
Expert Opinion on Therapeutic Patents 2018 November
INTRODUCTION: Farnesoid X receptor (FXR), a nuclear receptor mainly expressed in enterohepatic tissues, is a master for bile acid, lipid and glucose homeostasis. Additionally, it acts as a cell protector with unclear mechanism but may be implicated in combating against inflammation, fibrosis and cancers. FXR is thus accepted as a promising target particularly for the enterohepatic diseases, and numerous FXR modulators have been patented and developed.
AREAS COVERED: This review provides an update on the development of FXR modulators for enterohepatic diseases and offers an in-depth perspective on new strategies for the development of novel FXR modulators.
EXPERT OPINION: Despite the development of numerous FXR modulators, which culminated in the successful launch of obeticholic acid (OCA), it remains a matter of debate on how the function of FXR should be exploited for therapeutic purposes. The improvement for obesity achieved by either FXR agonists or antagonists is still in confusion. Whether the side effect of pruritus induced by OCA could be exempted for non-steroidal FXR agonists needs further validation. Apart from the development of conventional FXR ligands, emerging evidence support that restoration of FXR protein level may represent a new strategy in targeting FXR for enterohepatic and metabolic diseases.
AREAS COVERED: This review provides an update on the development of FXR modulators for enterohepatic diseases and offers an in-depth perspective on new strategies for the development of novel FXR modulators.
EXPERT OPINION: Despite the development of numerous FXR modulators, which culminated in the successful launch of obeticholic acid (OCA), it remains a matter of debate on how the function of FXR should be exploited for therapeutic purposes. The improvement for obesity achieved by either FXR agonists or antagonists is still in confusion. Whether the side effect of pruritus induced by OCA could be exempted for non-steroidal FXR agonists needs further validation. Apart from the development of conventional FXR ligands, emerging evidence support that restoration of FXR protein level may represent a new strategy in targeting FXR for enterohepatic and metabolic diseases.
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