GSK2332255B is a highly potent and selective TRPC3 and TRPC6 antagonist, exhibiting IC50 values of 5 nM and 4 nM for rat TRPC3 and rat TRPC6, respectively. Furthermore, GSK2332255B demonstrates exceptional selectivity, surpassing a ≥100-fold difference when compared to other calcium-permeable channels.

TRPC6 (rat):4 nM (IC50), TRPC3 (rat):5 nM (IC50)

GSK255B effectively inhibits the activation of Nuclear Factor of Activated T-cells (NFAT) by Angiotensin II (Ang II) in a dose-dependent manner in HEK293T cells overexpressing TRPC3, with concentrations of 0.01, 0.1, and 1 μM being tested. This inhibitory effect extends to HEK293T cells expressing a mutant TRPC6 channel, where the amino acids T70 and S322 are mutated to glutamic acid (SETE)[1]. Additionally, at a concentration of 10 μM, GSK255B prevents calcium influx induced by 20 μM Phenylephrine in rat neonatal cardiac myocytes. The compound also blocks the signaling pathways leading to cell hypertrophy triggered by either angiotensin II or endothelin-1 in both HEK293T cells and cardiac myocytes from neonatal and adult rats[1].