Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMM0PDO)

• Drug Name: Dalfampridine Drug Info
• Synonyms: Ampyra (TN)

Indication

Disease Entry	ICD 11	Status	REF
Multiple sclerosis	8A40	Approved	[1]

• Cross-matching ID:
  PubChem CID: 1727
  ChEBI ID: CHEBI:34385
  CAS Number: CAS 504-24-5
  TTD Drug ID: DMM0PDO
  INTEDE Drug ID: DR0408
  ACDINA Drug ID: D00001

Molecule-Related Drug Atlas

Drug(s) Targeting Potassium channel unspecific (KC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[4]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[4]
Dronedarone	DMA8FS5	Angina pectoris	BA40	Approved	[5]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[4]
Amifampridine	DMK08L3	LambertEaton myasthenic syndrome	8C62	Approved	[6]
Minoxidil	DMA2Z4F	Alopecia	ED70	Approved	[4]
Pinacidil	DMRADYL	High blood pressure	BA00	Approved	[4]
Ibutilide	DMKXY2R	Atrial fibrillation	BC81.3	Approved	[4]
Diazoxide	DML1538	Congenital hyperinsulinism	5A4Y	Approved	[4]
Azimilide	DMUIBV8	Atrial fibrillation	BC81.3	Phase 3	[7]

Drug(s) Metabolized By Cytochrome P450 2E1 (CYP2E1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[8]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[9]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[10]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[11]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[12]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[13]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[14]
Estrone	DM5T6US	Acne vulgaris	ED80	Approved	[15]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[16]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[17]

Drug(s) Affected By Potassium voltage-gated channel subfamily H member 2 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[18]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[19]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[20]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[21]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[21]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[22]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[23]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[24]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[25]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Potassium channel unspecific (KC)	TT1VOHK	NOUNIPROTAC	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2E1 (CYP2E1) Main DME	DEVDYN7	CP2E1_HUMAN	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[3]

References

• [1] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [2] Dalfampridine: a medication to improve walking in patients with multiple sclerosis. Ann Pharmacother. 2012 Jul-Aug;46(7-8):1010-5.
• [3] Effects of 4-Aminopyridine on Cloned hERG Channels Expressed in Mammalian Cells. Arch Drug Inf. 2009 Sep;2(3):51-57. doi: 10.1111/j.1753-5174.2009.00021.x.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [6] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [7] Azimilide. Drugs. 2000 Feb;59(2):271-7; discussion 278-9.
• [8] Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G54-63.
• [9] Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int. 2003 May;63(5):1687-96.
• [10] Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
• [11] Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 2010 Mar;44(3):340-55.
• [12] A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300.
• [13] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [14] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [15] Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P-450. Drug Metab Dispos. 2000 Feb;28(2):110-2.
• [16] Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol. 2002 Oct 1;64(7):1151-6.
• [17] CYP2E1 and clinical features in alcoholics. Neuropsychobiology. 2003;47(2):86-9.
• [18] Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
• [19] Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. doi: 10.1046/j.1540-8167.2005.04470.x.
• [20] Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.
• [21] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [22] Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol. 2008 Nov;155(6):957-66. doi: 10.1038/bjp.2008.325. Epub 2008 Aug 25.
• [23] Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
• [24] Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar;359(3):212-9. doi: 10.1007/pl00005344.
• [25] Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000 May 26;474(1):111-5. doi: 10.1016/s0014-5793(00)01586-6.