ICA-121431

• CAT Number: I003109
• CAS Number: 313254-51-2
• Molecular Formula: C23H19N3O3S2
• Molecular Weight: 449.55
• Purity: ≥95%
• Synonyms: 2,2-diphenyl-N-[4-(1,3-thiazol-2-ylsulfamoyl)phenyl]acetamide
• InChI: InChI=1S/C23H19N3O3S2/c27-22(21(17-7-3-1-4-8-17)18-9-5-2-6-10-18)25-19-11-13-20(14-12-19)31(28,29)26-23-24-15-16-30-23/h1-16,21H,(H,24,26)(H,25,27)
• InChIKey: URSQNPPONHUJDL-UHFFFAOYSA-N
• SMILES: C1=CC=C(C=C1)C(C2=CC=CC=C2)C(=O)NC3=CC=C(C=C3)S(=O)(=O)NC4=NC=CS4

ICA-121431 is a nanomolar potent and broad-spectrum voltage-gated sodium channel (Nav) blocker, shows equipotent selectivity for human Nav1.1 and Nav1.3 subtypes with IC50 values of 13 nM and 23 nM, respectively. ICA-121431 shows less potent inhibition of Nav1.2 (IC50=240 nM) and 1,000 fold selectivity against Nav1.4, Nav1.6, and the TTX-resistant human Nav1.5 and Nav1.8 channels (IC50s >10 µM).
ICA-121431 interacts with human Nav1.3 and the amino acid residues that may define selectivity for this channel over other related Nav channels, including Nav1.7 and Nav 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 hNav1.3 hNav1.5 hNav1.7 with IC50s of 0.013 µM, >30 µM, 12 µM, respectively[1].
ICA-121431 is against hNav channels with point mutations,shows hNav1.3 M1 (S1510Y), hNav1.3 M2 (R1511W), hNav1.3 M3 (E1559D), hNav1.3 M1,3 (S1510Y/E1559D), hNav1.3 M2, 3 (R1511W/E1559D), hNav1.3 M1, 2, 3 (S1510Y/R1511W/E1559D), and hNav1.7 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 hNav channels with point mutations,shows
hNav1.3/hNav1.5 S1-S4, hNav1.3/hNav1.5 S3-S4, hNav1.3/hNav1.5 S5-S6, hNav1.3/hNav1.7 S1, hNav1.3/hNav1.7 S2, hNav1.3/hNav1.7 S3-S4, and hNav1.3/hNav1.7 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].

Reference

[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.
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