Pico145 (HC-608) is a remarkable inhibitor of TRPC1/4/5 channels, specifically inhibiting ( )-englerin A-activated TRPC4/TRPC5 channels with IC50s of 0.349 and 1.3 nM in cells, while showing no effect on TRPC3, TRPC6, TRPV1, TRPV4, TRPA1, TRPM2, or TRPM8.

TRPC5:1.3 nM (cell assay), TRPC4:0.349 nM (cell assay), TRPC4-TRPC1:0.03 nM (cell assay), TRPC5-TRPC1:0.2 nM (cell assay)

Pico145 is a remarkable small-molecule inhibitor of TRPC1/4/5 channels. Pico145 displays no effect on TRPC3, TRPC6, TRPV1, TRPV4, TRPA1, TRPM2, TRPM8. Pico145 inhibits (?)-englerin A-activated TRPC4/TRPC5 channels (IC50s: 0.349 and 1.3 nM in cells). Pico145 also inhibits human TRPC4-TRPC1 and TRPC5-TRPC1 concatemers expressed in HEK 293 Tet+ cells (IC50, 0.03 nM, and 0.2 nM, respectively). Pico145 effectively inhibits RPC4-TRPC1 channels activated by sphingosine 1-phosphate (S1P) and suppresses S1P-evoked Ca2+ entry through TRPC4-TRPC1 channels (IC50: 0.011 nM). The potency of Pico145 can be reduced by increased (?)-englerin A concentration. Pico145 also sensitizes EA-sensitive cancer cell line (Hs578T cells) (IC50, 0.11 nM). Pico145 (100 nM) lacks effect on store-operated Ca2+ entry and histamine-evoked Ca2+ entry into endothelial cells[1].