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

General Information of Drug (ID: DMV23GL)

• Drug Name: LIDOFLAZINE Drug Info
• Synonyms: LIDOFLAZINE; Ordiflazine; Corflazine; Clinium; Lidoflazinum; Lidoflazin; 3416-26-0; Klinium; Angex; Lidoflazina [Italian]; McN-JR 7904; UNII-J4ZHN3HBTE; Lidoflazinum [INN-Latin]; Lidoflazina [INN-Spanish]; Lidoflazine [USAN:INN:BAN]; C30H35F2N3O; J4ZHN3HBTE; EINECS 222-312-8; R 7904; BRN 0904339; CHEMBL92870; MCN-JR-7904; 4-(4,4-Bis(p-fluorophenyl)butyl)-1-piperazineaceto-2',6'-xylidide; 1-Piperazineacetamide, 4-(4,4-bis(4-fluorophenyl)butyl)-N-(2,6-dimethylphenyl)-; NCGC00016627-01; NCGC00016627-04; CAS-3416-26-0

Indication

Disease Entry	ICD 11	Status	REF
Angina pectoris	BA40	Approved	[1]

• Cross-matching ID:
  PubChem CID: 3926
  ChEBI ID: CHEBI:93095
  CAS Number: CAS 3416-26-0
  TTD Drug ID: DMV23GL
  VARIDT Drug ID: DR00834
  INTEDE Drug ID: DR0957

Molecule-Related Drug Atlas

Drug(s) Targeting Solute carrier family 29 member 1 (SLC29A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
N6-CYCLOPENTYLADENOSINE	DMD6AJO	Discovery agent	N.A.	Investigative	[6]
Dilazep	DMOD5Y0	Discovery agent	N.A.	Investigative	[7]
S6-nitrobenzyl mercaptopurine riboside	DMIKJNL	Discovery agent	N.A.	Investigative	[8]
[3H]nitrobenzylmercaptopurine ribonucleoside	DM5TDFQ	Discovery agent	N.A.	Investigative	[9]
KF24345	DMK6SMW	Discovery agent	N.A.	Investigative	[10]
NBTGR	DMVF420	Discovery agent	N.A.	Investigative	[9]
9-Benzyl-6-(4-nitro-benzylsulfanyl)-9H-purine	DMNY5P1	Discovery agent	N.A.	Investigative	[11]
Nitrobenzylthioinosine	DM7F3RY	Discovery agent	N.A.	Investigative	[12]
6-(4-Nitro-benzylsulfanyl)-9-phenethyl-9H-purine	DMPL5XV	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting Sodium channel unspecific (NaC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[13]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[14]
Zonisamide	DM0DTF7	Alcohol dependence	6C40.2	Approved	[15]
Eslicarbazepine	DMZREFQ	Seizure disorder	8A6Z	Approved	[16]
LOMERIZINE	DME0TC8	Migraine	8A80	Approved	[17]
Levobupivacaine	DM783CH	Anaesthesia	9A78.6	Approved	[18]
Tetrodotoxin	DMWMPRG	Bacterial infection	1A00-1C4Z	Approved	[19]
Permethrin	DMZ0Q1G	Pediculus capitis infestation	1G00.0	Approved	[20]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[21]
Butacaine	DM584TM	Pain	MG30-MG3Z	Approved	[22]

Drug(s) Targeting Voltage-gated sodium channel alpha Nav1.3 (SCN3A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aryl carboxamide derivative 1	DMTZRCW	N. A.	N. A.	Patented	[23]
Aryl carboxamide derivative 2	DM146TA	N. A.	N. A.	Patented	[23]
Pyrimidine derivative 1	DMN9VQM	N. A.	N. A.	Patented	[23]
Pyrrolo-pyridinone derivative 6	DMXGNP8	N. A.	N. A.	Patented	[23]
Pyrrolo-pyridinone derivative 5	DMK2FSY	N. A.	N. A.	Patented	[23]
SIPATRIGINE	DMMQ4GC	Neurological disorder	6B60	Discontinued in Phase 2	[24]
U-92032	DMTYO3P	N. A.	N. A.	Terminated	[25]
PD-85639	DMNUKB4	N. A.	N. A.	Terminated	[2]
batrachotoxin	DMYH9SU	Discovery agent	N.A.	Investigative	[26]
veratridine	DMUF8JZ	Discovery agent	N.A.	Investigative	[26]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[27]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[28]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[29]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[30]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[31]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[32]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[33]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[34]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[28]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[35]

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	[36]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[37]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[38]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[39]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[39]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[40]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[41]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[42]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[43]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[39]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Inhibitor	[2]
Solute carrier family 29 member 1 (SLC29A1)	TTLXAKE	S29A1_HUMAN	Inhibitor	[3]
Voltage-gated sodium channel alpha Nav1.3 (SCN3A)	TTAXZ0K	SCN3A_HUMAN	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

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	[5]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Synthesis and pharmacological evaluation of phenylacetamides as sodium-channel blockers. J Med Chem. 1994 Jan 21;37(2):268-74.
• [3] Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibit... J Med Chem. 2007 Aug 9;50(16):3906-20.
• [4] Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. Curr Pharm Biotechnol. 2012 Jul;13(9):1705-17.
• [5] Comparative evaluation of HERG currents and QT intervals following challenge with suspected torsadogenic and nontorsadogenic drugs. J Pharmacol Exp Ther. 2006 Mar;316(3):1098-106. doi: 10.1124/jpet.105.093393. Epub 2005 Nov 8.
• [6] Inhibition of nucleoside transport proteins by C8-alkylamine-substituted purines. J Med Chem. 2005 Jan 13;48(1):321-9.
• [7] Residues Met89 and Ser160 in the human equilibrative nucleoside transporter 1 affect its affinity for adenosine, guanosine, S6-(4-nitrobenzyl)-merc... Mol Pharmacol. 2005 Mar;67(3):837-44.
• [8] Synthesis and biological evaluation of phloridzin analogs as human concentrative nucleoside transporter 3 (hCNT3) inhibitors. Bioorg Med Chem Lett. 2009 Feb 1;19(3):917-21.
• [9] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1117).
• [10] Interaction of the novel adenosine uptake inhibitor 3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazol... J Pharmacol Exp Ther. 2004 Mar;308(3):1083-93.
• [11] Inhibition of nucleoside transport by new analogues of 4-nitrobenzylthioinosine: replacement of the ribose moiety by substituted benzyl groups. J Med Chem. 2004 Oct 21;47(22):5441-50.
• [12] The role of human nucleoside transporters in uptake of 3'-deoxy-3'-fluorothymidine. Mol Pharmacol. 2008 Nov;74(5):1372-80.
• [13] Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders. CNS Drugs. 2009;23(7):555-68.
• [14] Sidedness of carbamazepine accessibility to voltage-gated sodium channels. Mol Pharmacol. 2014 Feb;85(2):381-7.
• [15] Antiepileptic drugs and relapse after epilepsy surgery. Epileptic Disord. 2008 Sep;10(3):193-8.
• [16] Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res. 2009 Jan;83(1):1-43.
• [17] Medicinal chemistry of neuronal voltage-gated sodium channel blockers. J Med Chem. 2001 Jan 18;44(2):115-37.
• [18] Block of neuronal tetrodotoxin-resistant Na+ currents by stereoisomers of piperidine local anesthetics. Anesth Analg. 2000 Dec;91(6):1499-505.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] In vitro assays for repellents and deterrents for ticks: differing effects of products when tested with attractant or arrestment stimuli. Med Vet Entomol. 2003 Dec;17(4):370-8.
• [21] Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.
• [22] WO patent application no. 2008,0857,11, Synergy of sodium channel blockers and calcium channel blockers.
• [23] Sodium channel blockers: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):279-90.
• [24] Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as use-dependent sodium channel blockers for the treatment of stroke. J Med Chem. 2002 Aug 15;45(17):3755-64.
• [25] Discovery of (2S)-1-(4-amino-2,3,5- trimethylphenoxy)-3-[4-[4-(4- fluorobenzyl)phenyl]-1-piperazinyl]-2-propanol dimethanesulfonate (SUN N8075): a ... J Med Chem. 2000 Sep 7;43(18):3372-6.
• [26] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 580).
• [27] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [28] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [29] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [30] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [31] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [32] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [33] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [34] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [35] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [36] 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.
• [37] 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.
• [38] 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.
• [39] 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.
• [40] 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.
• [41] 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.
• [42] 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.
• [43] 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.