Canonical transient receptor potential (TRPC) channels control influxes of Ca²⁺ and are activated upon stimulation of plasma membrane receptors coupled to phospholipase C. Among the TRPC subfamily members, TRPC3 and TRPC6 channels are directly activated by diacylglycerol (DAG) and function as signal transducers in vitro and in vivo, mediating promotion of neuronal survival and dendric outgrowth, and modulation of organ fibrosis. As evidenced by their pathophysiological roles, applications of TRPC3/6-targeting compounds for therapeutic use are highly anticipated. Here, we identified two compounds (L-687 and L-862) targeting TRPC3/C6 channels. First, we characterized L-862 which strongly and selectively inhibited TRPC3 (IC₅₀ =0.7 μM) and TRPC6 (IC₅₀ =4.6 μM) in a dose-dependent manner. L-862 also suppressed TGF-β-induced fibrosis in dermal fibroblasts. In addition, L-862 exhibited excellent in vivo pharmacokinetics and safety profiles, and showed efficacy in various fibrotic disease model animals. Secondly, we identified L-687 which selectivity activates TRPC3/C6/C7. Using L-687, we discovered a totally new function of TRPCs-activator in terms of trafficking of antisense oligonucleotides (ASOs) in the targeting cells. Namely, we found that co-administration of L-687 with ASO enhanced efficiency of ASO-mediated transcript knockdown. This finding would provide a chance of developing an unprecedented drug delivery system for ASO. In the presentation, new aspects of the physiological roles of TRPC3/C6 will also be discussed in more detail.