compound-326

Compound-326 is a potent, selective, and orally available small molecule inhibitor of Delta-5 desaturase (D5D), an enzyme encoded by the *Fads1* gene. D5D is the rate-limiting enzyme responsible for converting dihomo-γ-linolenic acid (DGLA) to arachidonic acid (AA) in the ω-6 polyunsaturated fatty acid pathway. Developed by Takeda Pharmaceutical Company, compound-326 modulates the eicosanoid profile by decreasing the production of pro-inflammatory AA-derived eicosanoids (such as prostaglandins and leukotrienes) while increasing the production of anti-inflammatory DGLA-derived eicosanoids. In preclinical studies using Western-diet fed ApoE knockout mice, oral administration of compound-326 significantly inhibited the progression of atherosclerotic lesions without affecting plasma total cholesterol or triglyceride levels, suggesting its potential as a novel remedy for preventing atherosclerosis and subsequent cardiovascular events.

Other names

2-(2,2,3,3,3-pentafluoropropoxy)-3-[4-(2,2,2-trifluoroethoxy)phenyl]-5,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-4,6-dione