AZ194 is a first-in-class, orally active inhibitor of CRMP2-Ubc9 interaction and inhibitor of NaV1.7 (IC50=1.2 μM). AZ194 blocks SUMOylation of CRMP2 to selectively reduce the amount of surface-expressed NaV1.7. Antinociceptive effects[1].
AZ194 would provide pain relief in rat models of chemotherapy- and nerve injury- induced neuropathic pain. AZ194 (orally; at 2 and 10 mg/kg) restores mechanical sensitivity in animals with chemotherapy-induced and nerve injury-induced neuropathic nociception[1].AZ194 (10 mg/kg; ip; CD1 male mice) does not affect motor performance (open field). AZ194 synergizes with commonly used painkillers, engages NaV1.7-dependent endogenous opioid signaling[1].
[1]. Cai S, et al. Selective targeting of NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in rodents. Sci Transl Med. 2021;13(619):eabh1314.