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HC-070

產(chǎn)品活性：HC-070 是一種瞬時受體電位通道蛋白 4/5 (TRPC4/TRPC5) 拮抗劑，在細胞中，對 hTRPC5 和 hTRPC4 的 IC₅₀ 值分別為 9.3 nM 和 46 nM。

研究領(lǐng)域：Membrane Transporter/Ion Channel  |  Neuronal Signaling

作用靶點：TRP Channel

In Vitro: 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.

In Vivo: 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.

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