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

General Information of Drug (ID: DMTQF4A)

• Drug Name: Tenofovir alafenamide Drug Info
• Synonyms: Tenofovir Alafenamide (GS-7340); Tenofovir Alafenamide [USAN:INN]; UNII-EL9943AG5J; UNII-J4414G3BUK; Vemlidy; Tenofovir; UNII-W4HFE001U5; W4HFE001U5; (R)-(((1-(6-AMINO-9H-PURIN-9-YL)PROPAN-2-YL)OXY)METHYL)PHOSPHONIC ACID; (R)-(1-(6-amino-9H-purin-9-yl)propan-2-yloxy)methylphosphonic acid; (R)-9-(2-Phosphonomethoxypropyl)adenine; (R)-9-[2-(Phosphonomethoxy)propyl]adenine; (R)-PMPA; ({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid; 147127-20-6; 9-[(R)-2-(phosphonomethoxy)propyl]adenine; Apropovir; CHEBI:63625; D,L-Tenofovir; GS-1278; PMPA; PMPA gel; (S)-Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate; 379270-37-8; AK109983; EL9943AG5J; GS 7340; GS-7339; GS-7340; GS7340; J4414G3BUK; L-Alanine, N-((S)-(((1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-, 1-methylethyl ester; TENOFOVIR ALAFENAMIDE

Indication

Disease Entry	ICD 11	Status	REF
HIV infectious disease		Approved	[1]

• Cross-matching ID:
  PubChem CID: 9574768
  ChEBI ID: CHEBI:90926
  CAS Number: CAS 379270-37-8
  TTD Drug ID: DMTQF4A
  INTEDE Drug ID: DR1552

Molecule-Related Drug Atlas

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	[5]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[6]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[7]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[8]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[7]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[7]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[9]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[7]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[14]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[15]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[16]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[17]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[18]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]

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	[21]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[22]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[23]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[24]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[25]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[26]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[27]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[28]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[22]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[2]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[3]
Cathepsin A (CTSA)	DE14JZK	PPGB_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Pharmacokinetics of Tenofovir Alafenamide When Coadministered With Other HIV Antiretrovirals. J Acquir Immune Defic Syndr. 2018 Aug 1;78(4):465-472.
• [3] FDA label of Bictegravir, emtricitabine, and tenofovir alafenamide. The 2020 official website of the U.S. Food and Drug Administration.
• [4] Bictegravir/Emtricitabine/Tenofovir Alafenamide: a review in HIV-1 infection. Drugs. 2018 Nov;78(17):1817-1828.
• [5] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [6] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [7] 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.
• [8] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [9] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [10] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [11] 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.
• [12] Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
• [13] Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
• [14] The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
• [15] Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
• [16] Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
• [17] Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
• [18] The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
• [19] Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
• [20] Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
• [21] 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.
• [22] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [23] 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.
• [24] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [25] 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.
• [26] 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.
• [27] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [28] 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.
• [29] 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.