Description
AC1903 is an inhibitor of transient receptor potential canonical channel 5 (TRPC5; IC
50 = 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 (AT
1) receptor that cannot be inactivated and endocytosed. It also suppresses proteinuria as well as reduces pseudocyst formation and podocyte loss in an AT
1 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.
Uses
AC1903 is a TRPC5 inhibitor with valuable potential for the treatment of progressive kidney diseases. AC1903 inhibits TRPC5 ion channels and suppresses progressive kidney diseases via TRPC5-AT1R related genetic pathways. ?AC1903 also provides therapeutic benefit in a rat model of hypertensive proteinuric kidney disease.
References
1) Zhou?et al.?(2017),?A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models; Science,?358?1332
