Description:
IC50: 8.3 and 5.8 nM for hTRPM8 and rTRPM8, respectively
The transient receptor potential melastatin 8 (TRPM8), a member of the TRP melastatin sub-group, is known to play a role in cold hyperalgesia and cold allodynia caused by disease conditions such as chemotherapy-induced peripheral neuropathy (CIPN, using the agents oxaliplatin, vincristine, or paclitaxel), diabetic neuropathy, migraine and overactive bladder (OAB). RQ-00203078 is identified as a selective and orally active TRPM8 antagonist.
In vitro: In the menthol-induced calcium influx assay, RQ-00203078 is a novel and highly potent TRPM8 antagonist with human and rat IC50 values of 8.3 nM and 5.8 nM, respectively. RQ-00203078 was highly selective over other TRP channels [1].
In vivo: RQ-00203078 demonstrated excellent activity in vivo 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].
Clinical trial: Up to now, RQ-00203078 is still in the preclinical development stage.
Reference:
[1] Ohmi M, Shishido Y, Inoue T, Ando K, Fujiuchi A, Yamada A, Watanabe S, Kawamura K. Identification of a novel 2-pyridyl-benzensulfonamide derivative, RQ-00203078, as a selective and orally active TRPM8 antagonist. Bioorg Med Chem Lett. 2014 Dec 1;24(23):5364-8.