Aug. 22, 2023

Targeting 20-HETE/GPR75 via Selective CYP Inhibition: A 20+ Year-Old Kidney Program from Taisho


oral 20-hydroxyeicosatetraenoic acid synthesis inhibitor preclinical efficacy in mouse kidney fibrosis model from in-house screen and optimization J. Pharm. Exp. Ther., May 4, 2023 Taisho Pharmaceutical CO., JP


The arachidonic acid (AA) metabolite, 20-hydroxy-5,8,11,14-eicosatetranoic acid (20-HETE), has been extensively studied as a modulator of kidney function and a mediator of kidney diseases over decades. The receptor for 20-HETE, the G-coupled protein receptor GPR75, was only recently identified (2017), and GPR75/20-HETE pathway modulators are of industry interest in many disease areas including obesity (e.g. 2020 Regeneron patent filing) and kidney diseases (e.g. 2018 Taisho patent filing). While Taisho has published on 20-HETE synthesis inhibitors such as HET0016 as early as 2001, they have only recently patented and disclosed a novel series of oral 20-HETE synthesis inhibitors including TP0472993 intended to treat renal fibrosis.



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