Cayman AC1903

AC1903 is an inhibitor of transient receptor potential canonical channel 5 (TRPC5; IC₅₀ = 14.7 µM). It is selective for TRPC5 over TRPC4 and TRPC6 at concentrations up to 100 and 30 µM, respectively. It inhibits TRPC5 in a concentration-dependent manner in HEK293 cells when used at concentrations ranging from 1 to 100 µM. AC1903 (30 µM) inhibits angiotensin II-induced production of reactive oxygen species (ROS) in wild-type podocytes and podocytes expressing a mutant angiotensin II type 1 (AT₁) receptor that cannot be inactivated and endocytosed. It also suppresses proteinuria as well as reduces pseudocyst formation and podocyte loss in an AT₁ receptor transgenic rat model of kidney disease when administered at a dose of 50 mg/kg twice per day. In a model of hypertension-induced focal segmental glomerulosclerosis (FSGS) using Dahl salt-sensitive rats, AC1903 decreases the rate of proteinuria when administered at the beginning of a high-salt diet and prevents progression when administered one week following initiation of a high-salt diet.

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