E-4031

Quality 0.50 · 1 view · Updated 2 months ago

Chemical compound

title: "E-4031" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["herg-blocker", "potassium-channel-blockers", "disubstituted-pyridines", "piperidines", "aromatic-ketones", "n-phenylmethanesulfonamide-derivatives"] description: "Chemical compound" topic_path: "general/herg-blocker" source: "https://en.wikipedia.org/wiki/E-4031" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

| verifiedrevid = 366892602 | IUPAC_name = N-[4-[1-[2-(6-Methylpyridin-2-yl)ethyl]piperidine-4-carbonyl]phenyl] | image = E-4031.png | image_class = skin-invert-image | alt =

| tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = | routes_of_administration =

| bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion =

| IUPHAR_ligand = 2605 | CAS_number = 113558-89-7 | CAS_supplemental = 113559-13-0 (dihydrochloride) | UNII_Ref = | UNII = 1L1K8X5DF9 | ATCvet = | ATC_prefix = | ATC_suffix = | PubChem = 3185 | ChEMBL = 327980 | ChemSpiderID = 3073 | DrugBank =

| C=21 | H=27 | N=3 | O=3 | S=1 | synonyms = (1-[2-(6-methyl-2-pyridyl)ethyl]-4-(4-methylsulfonyl-aminobenzoyl)piperidine) | smiles = Cc1cccc(n1)CCN2CCC(CC2)C(=O)c3ccc(cc3)NS(=O)(=O)C | StdInChI = 1S/C21H27N3O3S/c1-16-4-3-5-19(22-16)12-15-24-13-10-18(11-14-24)21(25)17-6-8-20(9-7-17)23-28(2,26)27/h3-9,18,23H,10-15H2,1-2H3 | StdInChIKey = SRUISGSHWFJION-UHFFFAOYSA-N

E-4031 is an experimental class III antiarrhythmic drug that blocks potassium channels of the hERG-type.

Chemistry

E-4031 is a synthesized toxin that is a methanesulfonanilide class III antiarrhythmic drug.

Target

E-4031 acts on a specific class of voltage-gated potassium channels mainly found in the heart, the hERG channels. hERG channels (Kv11.1) mediate the IKr current, which repolarizes the myocardial cells. The hERG channel is encoded by ether-a-go-go related gene (hERG).

Mode of action

E-4031 blocks hERG-type potassium channels by binding to the open channels. Its structural target within the hERG-channel is unclear, but some other methanesulfonanilide class III antiarrhythmic drugs are known to bind to the S6 domain or C-terminal of the hERG-channel.

Reducing IKr in myocardial cells prolongs the cardiac action potential and thus prolongs the QT-interval. In non-cardiac cells, blocking Ikr has a different effect: it increases the frequency of action potentials.

Toxicity

As E-4031 can prolong the QT-interval, it can cause lethal arrhythmias.

Therapeutic use

E-4031 is solely used for research purposes. So far, one clinical trial has been conducted to test the effect of E-4031 on prolongation of the QT-interval.

References

References

  1. (April 2005). "Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells". Journal of Applied Physiology.
  2. (March 1990). "4'-[(4-Piperidyl)carbonyl]methanesulfonanilides as potent, selective, bioavailable class III antiarrhythmic agents". Journal of Medicinal Chemistry.
  3. (January 2010). "Pharmacological removal of human ether-à-go-go-related gene potassium channel inactivation by 3-nitro-N-(4-phenoxyphenyl) benzamide (ICA-105574)". Molecular Pharmacology.
  4. (2008). "Human ether-a-go-go related gene (hERG) K+ channels: function and dysfunction". Progress in Biophysics and Molecular Biology.
  5. (1997). "The class III antiarrhythmic agent E-4031 selectively blocks the inactivating inward-rectifying potassium current in rat anterior pituitary tumour cells (GH3/B6 cells).". Pflügers Archiv.
  6. (July 1990). "Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents". The Journal of General Physiology.
  7. (March 1996). "Class III antiarrhythmic drugs block HERG, a human cardiac delayed rectifier K+ channel. Open-channel block by methanesulfonanilides". Circulation Research.
  8. (February 2000). "Molecular determinant of high-affinity dofetilide binding to HERG1 expressed in Xenopus oocytes: involvement of S6 sites". Molecular Pharmacology.
  9. (October 2000). "A structural basis for drug-induced long QT syndrome". Proceedings of the National Academy of Sciences of the United States of America.
  10. (August 2001). "Open channel block of HERG K(+) channels by vesnarinone". Molecular Pharmacology.
  11. (June 2002). "Molecular determinants of voltage-dependent human ether-a-go-go related gene (HERG) K+ channel block". The Journal of Biological Chemistry.
  12. (May 2003). "Voltage-dependent profile of human ether-a-go-go-related gene channel block is influenced by a single residue in the S6 transmembrane domain". Molecular Pharmacology.
  13. (August 2004). "Structural determinants of HERG channel block by clofilium and ibutilide". Molecular Pharmacology.
  14. (November 1992). "Differential effects of the new class III antiarrhythmic agents almokalant, E-4031 and D-sotalol, and of quinidine, on delayed rectifier currents in guinea pig ventricular myocytes". Cardiovascular Research.
  15. (January 1996). "Assessment of reverse use-dependent blocking actions of class III antiarrhythmic drugs by 24-hour Holter electrocardiography". Journal of the American College of Cardiology.

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::

herg-blockerpotassium-channel-blockersdisubstituted-pyridinespiperidinesaromatic-ketonesn-phenylmethanesulfonamide-derivatives