E-4031 dihydrochloride

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Background

E-4031 dihydrochloride is a methanesulfonanilide class Ⅲ antiarrhythmic agent, capable of prolonging cardiac action potential duration by blocking members of the ether-a-go-go-related gene (ERG) K+ channel family (IC50 = 29 nM). E-4031 dihydrochloride inhibits a variety of ERG isoforms, with KD values being 99, 116 and 193 nM for ERG1, ERG2 and ERG3, respectively. Voltage-gated potassium ERG channels regulate the inwardly rectifying K+ current that repolarizes myocardial cells, gut smooth muscle cells, as well as interstitial cells of Cajal. E-4031 dihydrochloride, as a human ERG (hERG; also known as Kv11.1) K+ channel blocker, has been used to pharmacologically rescue misprocessed hERG mutations in the long QT syndrome type 2.

1. Du LP, Tsai KC, Li MY, et al. The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents. Bioorganic & Medicinal Chemistry Letters, 2004, 14(18): 4771-4777.
2. Shi W, Wymore RS, Wang HS, et al. Identification of two nervous system-specific members of the erg potassium channel gene family. Journal of Neuroscience, 1997, 17(24): 9423-9432.
3. White EJ, Park SJ, Foster JA, et al. Ether-a-go-go-related gene 3 is the main candidate for the E-4031-sensitive potassium current in the pacemaker interstitial cells of Cajal. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2008, 295(4): G691-699.
4. Ficker E, Obejero-Paz CA, Zhao S, et al. The binding site for channel blockers that rescue misprocessed human long QT syndrome type 2 ether-a-gogo-related gene (HERG) mutations. Journal of Biological Chemistry, 2002, 277(7): 4989-4998.
5. Fujiki A. Electrophysiological effects of E-4031, a novel class Ⅲ antiarrhythmic agent. Cardiovascular Drun Reviews, 1994, 12(2): 165-172.