TRPC3 Inhibitor

Pyr10 is a pyrazole derivative and a selective TRP cation 3 (TRPC3) inhibitor. Pyr10 inhibits Ca²⁺ influx in carbachol-stimulated TRPC3-transfected HEK293 cells with an IC₅₀ of 0.72 μM (IC₅₀ of 13.08 μM for store operated Ca²⁺ entry in BRL-2H3 cells). Pyr10 has the ability to distinguish between receptor-operated TRPC3 and native stromal interaction molecule 1 (STIM1)/Orai1 channels.

Larixyl acetate is a potent and selective TRPC6 inhibitor with IC₅₀ values of 0.58 μM and 6.83 μM against hTRPC6-YFP and hTRPC3-YFP, respectively. Larixyl acetate prevents HPV and is effective in protecting against traumatic brain injury-induced systemic endothelial dysfunction.

GFB-8438 is a potent and subtype selective TRPC5 inhibitor, with IC₅₀s of 0.18 and 0.29 μM of hTRPC5 and hTRPC4, respectively. GFB-8438 shows excellent selectivity against TRPC6, other TRP family members, NaV 1.5, as well as limited activity against the hERG channel. GFB-8438 protects mouse podocytes from injury induced by protamine sulfate model.

Phenamil methanesulfonate, an analog of Amiloride (HY-B0285), is a more potent and less reversible epithelial sodium channel (ENaC) blocker with an IC₅₀ of 400 nM. Phenamil methanesulfonate is also a competive inhibitor of TRPP3 and inhibits TRPP3-mediated Ca²⁺ transport with an IC₅₀ of 140 nM in a Ca²⁺ uptake assay. Phenamil methanesulfonate is an intriguing small molecule to promote bone repair by strongly activating BMP signaling pathway. Phenamil methanesulfonate is used for the research of cystic fibrosis lung disease.

JW-65 is a selective TRPC3 channel inhibitor with favorable blood-brain barrier penetration. JW-65 directly binds to human TRPC3 protein and modulates calcium signaling to reduce seizure susceptibility. JW-65 reduces seizure incidence, severity, and duration while prolonging seizure latency in multiple seizure models. JW-65 alleviates Aβ‑induced neuronal damage. JW-65 serves as a valuable tool for research on epilepsy, seizure disorders, and Alzheimer’s disease.

TRPC3/6-IN-1 is a potent selectivity blocker of the canonical transient receptor channels (TRPC3/6), has block potency for hTRPC3 and hTRPC6 with IC₅₀ values of 1260 nM and 500 nM, respectively. TRPC3/6-IN-1 can be used for the research of chronic models of heart failure.