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

General Information of Drug (ID: DM29GAD)

• Drug Name: Lumefantrine Drug Info
• Synonyms: Benflumetol; Coartem; Dl-Benflumelol; Lumefantrine (INN); Lumefantrine [INN:BAN]; (+-)-2,7-Dichloro-9-((Z)-p-chlorobenzylidene)-alpha((dibutylamino)methyl)fluorene-4-methanol; (+-)-2,7-Dichloro-9-((Z)-p-chlorobenzylidene)-alpha-((dibutylamino)methyl)fluorene-4-methanol; 2-(dibutylamino)-1-[(9Z)-2,7-dichloro-9-(4-chlorobenzylidene)-9H-fluoren-4-yl]ethanol; 2-(dibutylamino)-1-[(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylidene]fluoren-4-yl]ethanol; 2-Dibutylamino-1-[2,7-dichloro-9-(4-chloro-benzylidene)-9H-fluoren-4-yl]-ethanol; 2-Dibutylamino-1-{2,7-dichloro-9-[1-(4-chloro-phenyl)-meth-(Z)-ylidene]-9H-fluoren-4-yl}-ethanol

Indication

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[1]

• Cross-matching ID:
  PubChem CID: 6437380
  ChEBI ID: CHEBI:156095
  CAS Number: CAS 82186-77-4
  TTD Drug ID: DM29GAD
  INTEDE Drug ID: DR0992

Molecule-Related Drug Atlas

Drug(s) Targeting Sodium pump subunit alpha-1 (ATP1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Artemether	DM48QOT	Malaria	1F40-1F45	Approved	[2]
Acocantherin	DM7JT24	Atrial fibrillation	BC81.3	Approved	[4]
Chloroprocaine	DMSOQK1	Anaesthesia	9A78.6	Approved	[5]
Deslanoside	DMB3ZSK	Arrhythmia	BC9Z	Approved	[4]
Almitrine	DM0SYAN	Chronic obstructive pulmonary disease	CA22	Approved	[6]
Acetyldigitoxin	DMHAUO0	Congestive heart failure	BD10	Approved	[7]
Aluminium	DM6ECN9	Hyperhidrosis	EE00	Approved	[8]
UNBS-1450	DMR38M4	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
DIGITOXIGENIN	DM5AOFW	Discovery agent	N.A.	Investigative	[10]

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	[11]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[12]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[18]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[12]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[19]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sodium pump subunit alpha-1 (ATP1A1)	TTWK8D0	AT1A1_HUMAN	Binder	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cytochrome P450 3A5 (CYP3A5) Main DME	DEIBDNY	CP3A5_HUMAN	Substrate	[]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [3] Development of a paediatric physiologically based pharmacokinetic model to assess the impact of drug-drug interactions in tuberculosis co-infected malaria subjects: A case study with artemether-lumefantrine and the CYP3A4-inducer rifampicin. Eur J Pharm Sci. 2017 Aug 30;106:20-33.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Inhibition of the Na,K-ATPase of canine renal medulla by several local anesthetics. Pharmacol Res. 2001 Apr;43(4):399-403.
• [6] Almitrine, a new kind of energy-transduction inhibitor acting on mitochondrial ATP synthase. Biochim Biophys Acta. 1989 Aug 3;975(3):325-9.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] The inhibitory effect of aluminium on the (Na+/K+)ATPase activity of rat brain cortex synaptosomes. J Inorg Biochem. 2003 Sep 15;97(1):143-50.
• [9] Early downregulation of Mcl-1 regulates apoptosis triggered by cardiac glycoside UNBS1450. Cell Death Dis. 2015 Jun 11;6:e1782.
• [10] 17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity r... J Med Chem. 2000 Jun 15;43(12):2332-49.
• [11] 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.
• [12] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [13] 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.
• [14] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [15] 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.
• [16] 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.
• [17] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [18] 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.
• [19] 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.