ICA-121431

ICA-121431 is a nanomolar potent and broad-spectrum voltage-gated sodium channel (Na_v) blocker, shows equipotent selectivity for human Na_v1.1 and Na_v1.3 subtypes with IC₅₀ values of 13 nM and 23 nM, respectively. ICA-121431 shows less potent inhibition of Na_v1.2 (IC₅₀=240 nM) and 1,000 fold selectivity against Na_v1.4, Na_v1.6, and the TTX-resistant human Na_v1.5 and Na_v1.8 channels (IC₅₀s >10 μM). In Vitro: ICA-121431 interacts with human Na_v1.3 and the amino acid residues that may define selectivity for this channel over other related Na_v?channels, including Na_v1.7 and Na_v 1.5. Data generated using conventional patch clamp electrophysiological recording using a pulse protocol whereby a 20-ms test pulse is preceded by an 8-s step to a voltage that inactivated half of the channels^[1].
ICA-121431 is against Wild type hNa_v1.3 hNa_v1.5 hNa_v1.7 with IC₅₀s of 0.013 μM, >30 μM, 12 μM, respectively^[1].
ICA-121431 is against hNa_v channels with point mutations,shows hNa_v1.3 M1 (S1510Y), hNa_v1.3 M2 (R1511W), hNa_v1.3 M3 (E1559D), hNa_v1.3 M1,3 (S1510Y/E1559D), hNa_v1.3 M2, 3 (R1511W/E1559D), hNa_v1.3 M1, 2, 3 (S1510Y/R1511W/E1559D), and hNa_v1.7 M1, 2, 3 (Y1537S/W1538R/D1586E) with IC₅₀ values of 0.1 μM, 0.37 μM, 1.1 μM, 1.3 μM, 1.9 μM, 11.6 μM, 0.032 μM, respectively^[1].
ICA-121431 is against hNa_v channels with point mutations,shows hNa_v1.3/hNa_v1.5 S1-S4, hNa_v1.3/hNa_v1.5 S3-S4, hNa_v1.3/hNa_v1.5 S5-S6, hNa_v1.3/hNa_v1.7 S1, hNa_v1.3/hNa_v1.7 S2, hNa_v1.3/hNa_v1.7 S3-S4, and hNa_v1.3/hNa_v1.7 S5-S6 with IC₅₀ values of 0.083 μM, 1.2 μM, 11 μM, 2.0 μM, 0.045 μM, 0.030 μM, 0.30 μM, 1.0 μM, and 0.024 μM, respectively^[1].