RQ-00203078

RQ-00203078 is a highly selective, potent and orally active TRPM8 antagonist with IC₅₀s of 5.3 nM and 8.3 nM for rat and human TRPM8 channels, respectively. RQ-00203078 shows little inhibitory action against TRPV1, TRPA1, TRPV4, or TRPM2 channels^[1][2]. In Vitro: Intracellular Ca²⁺ imaging reveals that menthol induced both intracellular Ca²⁺ release and store-operated Ca²⁺ entry, with RQ-00203078 inhibiting each effect. RQ-00203078 (1-10 µM) inhibits HSC3 and HSC4 oral squamous carcinoma cell migration and invasion in vitro^[2]. In Vivo: RQ-00203078 (compound 36) demonstrates excellent in vivo activity in a dose dependent manner with an ED₅₀ value of 0.65 mg/kg in the Icilin-induced wet-dog shakes model in rats after oral administration^[1].
Excellent oral exposure of RQ-00203078 (compound 36) is confirmed independently in rat pharmacokinetics studies at 3 mg/kg (p.o.) administration, with a C_max value of 2300 ng/mL and 86% bioavailability^[1].