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

General Information of Drug (ID: DMGB035)

• Drug Name: Armodafinil Drug Info
• Synonyms: Nuvigil; 112111-43-0; (R)-Modafinil; (R)-(-)-Modafinil; CEP-10953; UNII-V63XWA605I; CRL 40982; CEP 10953; V63XWA605I; CHEMBL1201192; CHEBI:77590; 2-[(R)-(Diphenylmethyl)sulfinyl]acetamide; (-)-2-((R)-(Diphenylmethyl)sulfinyl)acetamide; (-)-2-[(r)-(diphenylmethyl)sulfinyl]acetamide; Armodafinil [USAN:INN]; armodafinilo; armodafinilum; l-Modafinil; Nuvigil (TN); (-)-(R)-modafinil; Armodafinil (USAN/INN); SCHEMBL34489; ZINC6156; ACE037; Armodafinil, > YFGHCGITMMYXAQ-LJQANCHMSA-N

Indication

Disease Entry	ICD 11	Status	REF
Malignant glioma	2A00.0	Approved	[1]
Methamphetamine dependence	6C46.2	Approved	[1]
Narcolepsy	7A20	Approved	[1]
Pain	MG30-MG3Z	Approved	[1]
Pediatric cancer	2A00-2F9Z	Approved	[2]
Postpoliomyelitis syndrome		Approved	[1]
Traumatic brain injury	NA07.Z	Approved	[1]

• Cross-matching ID:
  PubChem CID: 9690109
  ChEBI ID: CHEBI:77590
  CAS Number: CAS 112111-43-0
  TTD Drug ID: DMGB035
  VARIDT Drug ID: DR00998
  INTEDE Drug ID: DR0137
  ACDINA Drug ID: D00044

Molecule-Related Drug Atlas

Drug(s) Targeting Adrenergic receptor alpha-1D (ADRA1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxazosin	DM9PLRH	Benign prostatic hyperplasia	GA90	Approved	[6]
Alfuzosin	DMZVMKF	Benign prostatic hyperplasia	GA90	Approved	[7]
Moxisylyte	DMFCLYW	Erectile dysfunction	HA01.1	Approved	[8]
Terazosin	DM3JCVS	Benign prostatic hyperplasia	GA90	Approved	[9]
Bunazosin	DM4I8O7	Glaucoma/ocular hypertension	9C61	Approved	[10]
Trimazosin	DM1QLST	Congestive heart failure	BD10	Approved	[11]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[12]
DL-017	DMM8GZT	Hypertension	BA00-BA04	Phase 1	[13]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[14]
PMID30124346-Compound-LDT66	DMJMTNL	Benign prostatic hyperplasia	GA90	Patented	[14]

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	[15]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[16]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[22]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[23]

Drug(s) Metabolized By Cytochrome P450 3A5 (CYP3A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[24]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[25]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[26]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[27]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[28]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[29]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[31]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[32]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor alpha-1D (ADRA1D)	TT34BHT	ADA1D_HUMAN	Agonist	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[5]

References

• [1] Armodafinil FDA Label
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Mechanisms of modafinil: A review of current research. Neuropsychiatr Dis Treat. 2007 June; 3(3): 349-364.
• [4] Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin Pharmacokinet. 2008;47(1):61-74.
• [5] Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123-37.
• [6] The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43.
• [7] Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62(4):633-53.
• [8] Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5.
• [9] Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
• [10] Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage. Cardiovasc Drug Rev. 2005 Spring;23(1):43-56.
• [11] The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):142-50.
• [12] A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.
• [13] Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. J Cardiovasc Pharmacol. 2001 Dec;38(6):893-9.
• [14] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [15] 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.
• [16] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [17] 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.
• [18] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [19] 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.
• [20] 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.
• [21] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [22] 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.
• [23] 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.
• [24] Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
• [25] Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
• [26] Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
• [27] Drug Interactions Flockhart Table
• [28] Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
• [29] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [30] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [31] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [32] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.