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

General Information of Drug (ID: DML0B41)

• Drug Name: Naloxegol Drug Info
• Synonyms: NKTR-118

Indication

Disease Entry	ICD 11	Status	REF
Opioid-induced constipation	DB32.1	Approved	[1] , [2] , [3]

• Cross-matching ID:
  PubChem CID: 56959087
  ChEBI ID: CHEBI:82975
  CAS Number: CAS 854601-70-0
  TTD Drug ID: DML0B41
  VARIDT Drug ID: DR01266
  INTEDE Drug ID: DR1126
  ACDINA Drug ID: D00454

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[7]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[8]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[9]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[10]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[13]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[14]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Bacterial infection	1A00-1C4Z	Approved	[15]
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[16]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[17]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[18]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[17]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[17]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]

Drug(s) Targeting Opioid receptor mu (MOP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Buprenorphine	DMPRI8G	Pain	MG30-MG3Z	Approved	[22]
Morphine	DMRMS0L	Chronic pain	MG30	Approved	[23]
Hydromorphone	DMHP21E	Pain	MG30-MG3Z	Approved	[24]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[25]
Fentanyl	DM8WAHT	Analgesia	MB40.8	Approved	[26]
Alfentanil	DMVO0UB	Anaesthesia	9A78.6	Approved	[27]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[28]
Nalfurafine hcl	DMA9DHW	Uremic pruritus	EC90.10	Approved	[29]
Oxycodone	DMXLKHV	Pain	MG30-MG3Z	Approved	[30]
Methylnaltrexone bromide	DMZTGN2	Opioid-induced constipation	DB32.1	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Modulator	[2] , [3]

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) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[5]

References

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• [2] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [5] Naloxegol: treatment for opioid-induced constipation in chronic non-cancer pain. Ann Pharmacother. 2015 Mar;49(3):360-5.
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• [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] Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
• [23] Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord.J Pharmacol Exp Ther.2005 Sep;314(3):1101-8.
• [24] Clinical pipeline report, company report or official report of signaturerx.
• [25] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [26] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [27] Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001 Mar;91(1-2):177-87.
• [28] Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
• [29] Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology. Bioorg Med Chem Lett. 2010 Jan 1;20(1):121-4.
• [30] 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: 319).