2,2-Diphenyl-N-[4-(thiazol-2-ylsulfamoyl)-phenyl]-acetamide

Description

ICA 121431 is a voltage-gated sodium channel (Na_v) blocker that selectively blocks Na_v1.1 and Na_v1.3 over Na_v1.4, and Na_v1.5-1.8 channels (IC₅₀s = <20, 19, 240, and >10,000 nM, respectively). It induces a concentration-dependent hyperpolarizing shift in voltage dependence of inactivation of Na_v1.3 channels at a concentration 1 μM but has no effect on resting channels. Substitution of the Na_v1.3 domain IV voltage-sensor domain (VSD4) with the Na_v1.5 VSD4 reduces ICA 121431 potency by approximately 500-fold.

Uses

ICA 121431 is a voltage-gated sodium (Nav) channel inhibitor.

IC 50

hNa_v1.1: 13 nM (IC₅₀); hNa_v1.3: 23 nM (IC₅₀); hNa_v1.4: 240 nM (IC₅₀); hNa_v1.6: >10 μM (IC₅₀); hNa_v1.5: >10 μM (IC₅₀); hNa_v1.8: >10 μM (IC₅₀)

storage

+4°C

References

[1] KEN MCCORMACK. Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2013: E2724-32. DOI:10.1073/pnas.1220844110
[2] JEREMIAH D OSTEEN. Pharmacology of the Nav1.1 domain IV voltage sensor reveals coupling between inactivation gating processes.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017: 6836-6841. DOI:10.1073/pnas.1621263114