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

General Information of Drug (ID: DMBSHMF)

• Drug Name: BOCEPREVIR Drug Info
• Synonyms: Boceprevir; Victrelis; 394730-60-0; SCH 503034; EBP 520; UNII-89BT58KELH; SCH-503034; 89BT58KELH; CHEBI:68621; (1R,2S,5S)-N-(4-amino-1-cyclobutyl-3,4-dioxobutan-2-yl)-3-[N-(tert-butylcarbamoyl)-3-methyl-L-valyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide; 3-{[(1R,2S,5S)-3-[(2S)-2-[(tert-butylcarbamoyl)amino]-3,3-dimethylbutanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2-yl]formamido}-4-cyclobutyl-2-oxobutanamide

Indication

Disease Entry	ICD 11	Status	REF
Hepatitis C virus infection	1E51.1	Approved	[1]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[2]

• Cross-matching ID:
  PubChem CID: 10324367
  ChEBI ID: CHEBI:68621
  CAS Number: CAS 394730-60-0
  TTD Drug ID: DMBSHMF
  VARIDT Drug ID: DR01333
  INTEDE Drug ID: DR0218
  ACDINA Drug ID: D00073

Molecule-Related Drug Atlas

Drug(s) Targeting Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Simeprevir	DMLUA9D	Chronic HCV-1 infection	1E51.1	Approved	[7]
Telaprevir	DMMRV29	Hepatitis C virus infection	1E51.1	Approved	[3]
Glecaprevir; pibrentasvir	DMF6Z5T	Hepatitis C virus infection	1E51.1	Approved	[8]

Drug(s) Targeting COVID-19 3C-like protease (3CLpro)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-07817883	DMNX86H	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 1	[9]
GC376	DMR1CLY	Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[2]
GRL001	DM19T2V	Coronavirus infection	1D92	Preclinical	[10]

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	[11]
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	[13]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[13]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[16]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[17]

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	[18]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[20]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[21]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[22]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[23]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[24]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[25]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[19]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[26]

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	[27]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[28]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[29]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[30]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[31]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[32]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[33]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[34]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[35]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A)	TTHC7JD	POLG_HCV1	Modulator	[3]
COVID-19 3C-like protease (3CLpro)	TT1D53B	R1AB_SARS2 (3264-3569)	Inhibitor	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[6]

References

• [1] 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. (Ligand id: 7876).
• [2] Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. 2020. April 20. doi: https://doi.org/10.1101/2020.04.20.051581
• [3] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [4] Drug interactions and protease inhibitors used in the treatment of hepatitis C: how to manage? Eur J Clin Pharmacol. 2014 Jul;70(7):775-89.
• [5] Pharmacokinetic evaluation of the interaction between hepatitis C virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pravastatin. Antimicrob Agents Chemother. 2013 Jun;57(6):2582-8.
• [6] Direct-acting antiviral agents for hepatitis C virus infection. Annu Rev Pharmacol Toxicol. 2013;53:427-49.
• [7] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [8] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [9] ClinicalTrials.gov (NCT05580003) COVID-19: A MULTIPART, PHASE 1 STUDY WITH RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE-DOSE ESCALATION TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-07817883 AND OPTIONAL OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE RELATIVE BIOAVAILABILITY AND FOOD EFFECT OF SOLID ORAL FORMULATION AND OPTIONAL OPEN-LABEL, NON-RANDOMIZED STUDY TO EVALUATE METABOLISM AND EXCRETION OF PF-07817883 AND OPTIONAL RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE EFFECT OF PF-07817883 ON PHARMACOKINETICS OF MIDAZOLAM IN HEALTHY ADULT PARTICIPANTS. U.S.National Institutes of Health.
• [10] Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
• [11] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [12] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [13] 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.
• [14] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [15] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [16] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [17] 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.
• [18] 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.
• [19] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [20] 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.
• [21] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [22] 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.
• [23] 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.
• [24] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] 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.
• [30] Drug Interactions Flockhart Table
• [31] 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.
• [32] Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
• [33] Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
• [34] Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
• [35] Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.