Pyr10

Pyr10 is a pyrazole derivative and a selective TRP cation 3 (TRPC3) inhibitor. Pyr10 inhibits Ca²⁺ influx in carbachol-stimulated TRPC3-transfected HEK293 cells with an IC₅₀ of 0.72 μM (IC₅₀ of 13.08 μM for store operated Ca²⁺ entry in BRL-2H3 cells). Pyr10 has the ability to distinguish between receptor-operated TRPC3 and native stromal interaction molecule 1 (STIM1)/Orai1 channels^[1]. In Vitro: Pyr10 has the ability to discriminate between the classical Orai-mediated, highly Ca²⁺ selective signalling pathway and the phospholipase C-dependent Ca²⁺ entry-mediated by TRPC channels, specifically by TRPC3. Pyr10 (3 μM) completely eliminates TRPC3 currents as well as Ca²⁺ entry while exerting modest effects on Orai-mediated responses. The selective block of TRPC3 channels by Pyr10 barely affected mast cell activation^[1]. In Vivo: Genetic deletion (TRPC3^-/-) and pharmacological channel blockade with Pyr10 blunts ventricular cardiac fibroblast activation and myocardial fibrosis in N(ω)-nitro-l-arginine methyl ester (l-NAME) hypertensive mice^[2].