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

General Information of Drug (ID: DM4W9B3)

• Drug Name: Fosamprenavir Drug Info
• Synonyms: Telzir; Amprenavir phosphate; Fosamprenavir [INN]; GW 433908; GW433908; VX 175; Fosamprenavir (INN); Lexiva (TM); Lexiva (TN); Telzir (TN); Telzir(TM); VX-175; GW433908A (*Sodium Salt*); GW433908G (*Calcium Salt*); [(3S)-oxolan-3-yl] N-[(2S,3R)-4-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-1-phenyl-3-phosphonooxybutan-2-yl]carbamate; Carbamic acid, ((1S,2R)-3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-1-(phenylmethyl)-2-(phosphonooxy)propyl)-, C-((3S)-tetrahydro-3-furanyl) ester; ((3S)Oxolan-3-yloxy)-N-((1S,2R)-3-{[(4-aminophenyl)sulfonyl](2-methylpropyl)amino}-1-benzyl-2-(phosphonooxy)propyl)carboxamide; (3-(((4-Aminophenyl)sulfonyl)(2-methylpropyl)amino)-1-(phenylmethyl)-2-(phosphonooxy)propyl)carbamic acid C-(tetrahydro-3-furanyl) ester

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[1]

• Therapeutic Class: Anti-HIV Agents
• Cross-matching ID:
  PubChem CID: 131536
  ChEBI ID: CHEBI:82941
  CAS Number: CAS 226700-79-4
  TTD Drug ID: DM4W9B3
  VARIDT Drug ID: DR01274
  INTEDE Drug ID: DR0745
  ACDINA Drug ID: D00292

Molecule-Related Drug Atlas

Drug(s) Targeting Human immunodeficiency virus Protease (HIV PR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Saquinavir	DMG814N	Human immunodeficiency virus infection	1C62	Approved	[5]
Indinavir	DM0T3YH	Human immunodeficiency virus infection	1C62	Approved	[6]
Ritonavir	DMU764S	Human immunodeficiency virus infection	1C62	Approved	[7]
Atazanavir	DMSYRBX	Human immunodeficiency virus infection	1C62	Approved	[8]
Amprenavir	DMLMXE0	Human immunodeficiency virus infection	1C62	Approved	[9]
Darunavir	DMN3GCH	Human immunodeficiency virus infection	1C62	Approved	[10]
Tipranavir	DM8HJX6	Human immunodeficiency virus infection	1C62	Approved	[11]
BI 201335	DM3MXT8	Hepatitis C virus infection	1E51.1	Phase 3	[12]
BMS 650032	DMQI43G	Hepatitis C virus infection	1E51.1	Phase 2	[13]
Danoprevir	DM20MDU	Hepatitis C virus infection	1E51.1	Phase 2	[14]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[15]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[16]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[17]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[18]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]

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	[22]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[23]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[24]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[25]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[26]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[27]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[28]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[29]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[23]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Protease (HIV PR)	TT5FNQT	POL_HV1B1	Inhibitor	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[3]

Drug-Metabolizing Enzyme (DME)

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

References

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• [3] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [4] Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68.
• [5] PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. J Med Virol. 2008 Dec;80(12):2053-63.
• [6] Quantification of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cell lysate using liq... J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Feb 15;877(5-6):575-80.
• [7] Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr;33(4):307-20.
• [8] Hollow-fiber unit evaluation of a new human immunodeficiency virus type 1 protease inhibitor, BMS-232632, for determination of the linked pharmacod... J Infect Dis. 2001 Apr 1;183(7):1126-9.
• [9] Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503.
• [10] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] 2011 Pipeline of Boehringer Ingelheim Pharma.
• [13] 2011 Pipeline of Bristol-Myers Squibb.
• [14] 2011 Pipeline of InterMune.
• [15] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [16] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [17] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [18] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [19] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [20] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [21] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [22] 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.
• [23] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [24] 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.
• [25] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [26] 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.
• [27] 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.
• [28] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [29] 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.
• [30] 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.