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

General Information of Drug (ID: DMYILBE)

• Drug Name: Modafinil Drug Info
• Synonyms: Provigil; Modiodal

Indication

Disease Entry	ICD 11	Status	REF
Malignant glioma	2A00.0	Approved	[1]
Methamphetamine dependence	6C46.2	Approved	[1]
Narcolepsy	7A20	Approved	[2]
Pain	MG30-MG3Z	Approved	[1]
Postpoliomyelitis syndrome		Approved	[1]
Traumatic brain injury	NA07.Z	Approved	[1]
Bipolar disorder	6A60	Phase 4	[3]
Brain injury	NA07.Z	Investigative	[4]

• Therapeutic Class: Neurology Agents
• Cross-matching ID:
  PubChem CID: 4236
  ChEBI ID: CHEBI:77585
  CAS Number: CAS 68693-11-8
  TTD Drug ID: DMYILBE
  VARIDT Drug ID: DR00411
  INTEDE Drug ID: DR1104
  ACDINA Drug ID: D00442

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine transporter (DAT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[9]
Dasotraline	DMLDQFV	Attention deficit hyperactivity disorder	6A05.Z	Approved	[10]
Methylphenidate	DM7SJD6	Attention deficit hyperactivity disorder	6A05.Z	Approved	[11]
Phenmetrazine	DMXYTN9	Obesity	5B81	Approved	[12]
Ioflupane i-123	DMNARJT	Parkinson disease	8A00.0	Approved	[2]
DEXMETHYLPHENIDATE HYDROCHLORIDE	DM8WBAH	Attention deficit hyperactivity disorder	6A05.Z	Approved	[13]
Altropane	DMO9WDS	Attention deficit hyperactivity disorder	6A05.Z	Approved	[14]
Amitifadine	DMS1X67	Obesity	5B81	Phase 3	[15]
NAV5001	DMRSI1M	Dementia	6D80-6D86	Phase 3	[14]
MIN-117	DMSLIW6	Major depressive disorder	6A70.3	Phase 2	[16]

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	[17]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[18]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[19]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[21]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[23]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[24]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[18]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[25]

Drug(s) Affected By Catechol O-methyltransferase (COMT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[26]
Dobutamine	DMD1B8Z	Heart failure	BD10-BD13	Approved	[26]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[26]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[26]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[27]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[28]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[29]
Tolcapone	DM8MNVO	Parkinson disease	8A00.0	Approved	[30]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[31]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[32]

Drug(s) Affected By Sodium-dependent dopamine transporter (SLC6A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[33]
Amphetamine	DMSZQAK	Attention deficit hyperactivity disorder	6A05.Z	Approved	[34]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[35]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[36]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[37]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[37]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[31]
Dextroamphetamine	DMMIHVP	Attention deficit hyperactivity disorder	6A05.Z	Approved	[38]
Vorinostat	DMWMPD4	Adult acute monocytic leukemia		Approved	[39]
Permethrin	DMZ0Q1G	Pediculus capitis infestation	1G00.0	Approved	[40]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine transporter (DAT)	TTVBI8W	SC6A3_HUMAN	Modulator	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Catechol O-methyltransferase (COMT)	OTPWKTQG	COMT_HUMAN	Drug Response	[7]
Sodium-dependent dopamine transporter (SLC6A3)	OT39XG28	SC6A3_HUMAN	Drug Response	[8]

References

• [1] Modafinil FDA Label
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] ClinicalTrials.gov (NCT01965925) Targeting Circadian and Cognitive Dysfunction in Bipolar Disorder With Modafinil. U.S. National Institutes of Health.
• [4] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [7] Effects of modafinil on the sleep EEG depend on Val158Met genotype of COMT. Sleep. 2010 Aug;33(8):1027-35. doi: 10.1093/sleep/33.8.1027.
• [8] Dopaminergic role in regulating neurophysiological markers of sleep homeostasis in humans. J Neurosci. 2014 Jan 8;34(2):566-73. doi: 10.1523/JNEUROSCI.4128-13.2014.
• [9] Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.
• [10] Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults. Neuropsychopharmacology. 2015 Nov;40(12):2745-52.
• [11] Imaging the effects of methylphenidate on brain dopamine: new model on its therapeutic actions for attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1;57(11):1410-5.
• [12] Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. Eur J Pharmacol. 2002 Jun 28;447(1):51-7.
• [13] Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate. J Med Chem. 2007 May 31;50(11):2718-31.
• [14] Rapid detection of Parkinson's disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse. 1998 Jun;29(2):128-41.
• [15] 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: 927).
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] 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.
• [18] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [19] 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.
• [20] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [21] 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.
• [22] 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.
• [23] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [24] 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.
• [25] 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.
• [26] Molecular mechanisms controlling the rate and specificity of catechol O-methylation by human soluble catechol O-methyltransferase. Mol Pharmacol. 2001 Feb;59(2):393-402. doi: 10.1124/mol.59.2.393.
• [27] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [28] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [29] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [30] Tolcapone increases plasma catecholamine levels in patients with Parkinson's disease. Parkinsonism Relat Disord. 2001 Apr;7(2):93-96. doi: 10.1016/s1353-8020(00)00027-4.
• [31] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [32] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [33] Functional characterization of N-octyl 4-methylamphetamine variants and related bivalent compounds at the dopamine and serotonin transporters using Ca(2+) channels as sensors. Toxicol Appl Pharmacol. 2021 May 15;419:115513. doi: 10.1016/j.taap.2021.115513. Epub 2021 Mar 27.
• [34] Dopamine transporter gene associated with diminished subjective response to amphetamine. Neuropsychopharmacology. 2005 Mar;30(3):602-9. doi: 10.1038/sj.npp.1300637.
• [35] Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells. J Biol Chem. 2016 Oct 14;291(42):22053-22062. doi: 10.1074/jbc.M116.749119. Epub 2016 Aug 23.
• [36] Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in?vivo assays in mice. Neuropharmacology. 2016 Nov;110(Pt A):143-153. doi: 10.1016/j.neuropharm.2016.07.016. Epub 2016 Jul 20.
• [37] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [38] Pharmacological characterization of the aminorex analogs 4-MAR, 4,4'-DMAR, and 3,4-DMAR. Neurotoxicology. 2019 May;72:95-100. doi: 10.1016/j.neuro.2019.02.011. Epub 2019 Feb 15.
• [39] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [40] Pyrethroid pesticide-induced alterations in dopamine transporter function. Toxicol Appl Pharmacol. 2006 Mar 15;211(3):188-97. doi: 10.1016/j.taap.2005.06.003. Epub 2005 Jul 11.