HC-070 is an antagonist of TRPC4/TRPC5, with IC50s of 9.3 nM and 46 nM for hTRPC5 and hTRPC4 in cells, respectively.
HC-070 is an antagonist of TRPC4/TRPC5, with IC50s of 9.3 nM and 46 nM for hTRPC5 and hTRPC4, respectively. HC-070 weakly inhibits TRPC3 (IC50, 1 μM), and is at least 400-fold selective for human TRPC4 and TRPC5-containing channels versus the other channels examined. HC-070 inhibits lanthanum-activated hTRPC5-, mTRPC5-, rTRPC5-mediated currents with IC50s of 0.52 nM, 0.55 nM, and 0.32 nM in whole-cell manual patch clamp. Furthermore, HC-070 blocks M2R-activated human TRPC1/TRPC4 channels with an IC50 of 1.3 nM and La3+- and M1R-activated human TRPC1/5 channels with IC50s of 1.4 nM and 4.4 nM. HC-070 inhibits human TRPC5 currents activated via muscarinic type 1 (M1R) with an IC50 of 2.0 nM. HC-070 also suppresses hTRPC4 currents via M2R with an IC50 of 0.49 nM. HC-070 (20 nM) reduces CCK-4 evoked neuronal activity in the amygdala slices[1].
HC-070 (1 mg/kg, p.o.) affects mice with increased evoked anxiety (CCK-4), but shows no effects in the absence of CCK-4. HC-070 (0.3, 1 or 3 mg/kg, p.o.) decreases anxiety in a standard EPM (more light/high anxiety). HC-070 (1 mg/kg) reduces the increased capacity for fear memory in mice subjected to chronic social stress on days 1-15. In addition, HC-070 (1, 3, 10 mg/kg, p.o.) causes reduction in marble burying behavior. HC-070 (0.3, 1, 3, 10 mg/kg, p.o.) also reduces time of immobility in a tail suspension test but does not impact locomotor activity in mice[1].
[1]. Just S, et al. Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice. PLoS One. 2018 Jan 31;13(1):e0191225.