Biological Activity
BIM-46187 is an inhibitor of heterotrimeric G-protein signaling.1,2 It inhibits signaling through Gαi, Gαs, and Gαq in MZ7 cells but selectively inhibits Gαq in HEK293 and CHO cells, indicating cell-dependent inhibition.1 BIM-46187 (0.1-1 mg/kg) increases the paw withdrawal threshold to a mechanical stimulus in a rat model of carrageenan-induced hyperalgesia.3 It also reduces mechanical hyperalgesia in a rat model of neuropathic pain induced by chronic constriction injury (CCI) when administered at doses ranging from 0.3 to 3 mg/kg.
References
1.Schmitz, A.-L., Schrage, R., Gaffal, E., et al.A cell-permeable inhibitor to trap Gαq proteins in the empty pocket conformationChem. Biol.21(7)890-902(2014)
2.Zhang, H., Nielsen, A.L., and Str?mgaard, K.Recent achievements in developing selective Gq inhibitorsMed. Res. Rev.40(1)135-157(2019)
3.Favre-Guilmard, C., Zeroual-Hide, H., Soulard, C., et al.The novel inhibitor of the heterotrimeric G-protein complex, BIM-46187, elicits anti-hyperalgesic properties and synergizes with morphineEur. J. Pharmacol.594(1-3)70-76(2008)
