ICA-121431 is a nanomolar potent small molecule Nav1.7 channel inhibitor with IC50 of 19 nM for rat Nav1.7, but no inhibition on human, monkey and dog Nav1.7.IC50 value: 19 nM (rat Nav1.7) [1]Target: rat Nav1.7 inhibitorICA-121431 exhibited a spectrum of inhibitory activity for Nav human channel subtypes; equipotent inhibition of Nav1.3 and Nav1.1, less potent inhibition of Nav1.2, and much weaker inhibition of Nav1.7, Nav1.6, Nav1.4, and the TTX-resistant human Nav1.5 and Nav1.8 channels (IC50s >10 μM). the unique subtype selective Nav channel inhibitors ICA-121431 and PF-04856264 interact with amino acid residues on an extracellular facing region of the homologous Domain 4 voltage sensor of Nav1.3 or Nav1.7, which is distinct from previously described interaction sites for TTX or local anesthetic-like Nav channel inhibitors.
References:
[1]. McCormack K, et al. Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):E2724-32.