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Peer-reviewed veterinary case report

Discovery of XL335 (WAY-362450), a highly potent, selective, and orally active agonist of the farnesoid X receptor (FXR).

Journal:
Journal of medicinal chemistry
Year:
2009
Authors:
Flatt, Brenton et al.
Affiliation:
Department of Medicinal Chemistry · United States
Species:
rodent

Abstract

Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X receptor (FXR). In vitro and in vivo optimization has led to the discovery of 6m (XL335, WAY-362450) as a potent, selective, and orally bioavailable FXR agonist (EC(50) = 4 nM, Eff = 149%). Oral administration of 6m to LDLR(-/-) mice results in lowering of cholesterol and triglycerides. Chronic administration in an atherosclerosis model results in significant reduction in aortic arch lesions.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/19159286/