General Information of Drug (ID: DM0YROF)

Drug Name
Ethylmorphine
Synonyms
Ethylmorphine; Codethyline; DIONINE; 76-58-4; Morphine, ethyl-; Ethyl morphine; UNII-RWO67D87EU; Ethylmorphine [BAN]; 3-O-Ethylmorphine; EINECS 200-970-7; RWO67D87EU; CHEBI:4902; DEA No. 9190; Dionin; Ethylmorphine (BAN); NCGC00168251-01; Ethomorphine; Morphinan-6-alpha-ol, 7,8-didehydro-4,5-alpha-epoxy-3-ethoxy-17-methyl-; (4R,4aR,7S,7aR,12bS)-9-ethoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol; Morphine 3-ethyl ether; AC1Q37UW; Morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-ethoxy-17-methyl-
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 313.4
Topological Polar Surface Area (xlogp) 1.5
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
Metabolism
The drug is metabolized via the liver [2]
Chemical Identifiers
Formula
C19H23NO3
IUPAC Name
(4R,4aR,7S,7aR,12bS)-9-ethoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
Canonical SMILES
CCOC1=C2C3=C(C[C@@H]4[C@H]5[C@]3(CCN4C)[C@@H](O2)[C@H](C=C5)O)C=C1
InChI
InChI=1S/C19H23NO3/c1-3-22-15-7-4-11-10-13-12-5-6-14(21)18-19(12,8-9-20(13)2)16(11)17(15)23-18/h4-7,12-14,18,21H,3,8-10H2,1-2H3/t12-,13+,14-,18-,19-/m0/s1
InChIKey
OGDVEMNWJVYAJL-LEPYJNQMSA-N
Cross-matching ID
PubChem CID
5359271
ChEBI ID
CHEBI:4902
CAS Number
76-58-4
DrugBank ID
DB01466
TTD ID
D0N5QC
INTEDE ID
DR0661

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 Agonist [1]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [3]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [4]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [5]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [6]
Docosahexaenoic acid omega-hydroxylase (CYP4F11) DEIZLTN CP4FB_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Discovery agent
ICD Disease Classification N.A.
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Opioid receptor mu (MOP) DTT OPRM1 5.94E-01 -0.02 -0.17
Cytochrome P450 2B6 (CYP2B6) DME CYP2B6 5.79E-01 -1.30E-02 -9.78E-02
Docosahexaenoic acid omega-hydroxylase (CYP4F11) DME CYP4F11 6.86E-01 -4.38E-02 -2.46E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 5.64E-01 2.36E-02 1.75E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 6.06E-01 -2.42E-02 -1.64E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose. Br J Clin Pharmacol. 1995 Jun;39(6):611-20.
2 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
3 Metabolic activation of aromatic amines by human pancreas. Carcinogenesis. 1997 May;18(5):1085-92.
4 A sensitive LC-MS/MS assay for the determination of dextromethorphan and metabolites in human urine--application for drug interaction studies assessing potential CYP3A and CYP2D6 inhibition. J Pharm Biomed Anal. 2002 Aug 22;30(1):113-24.
5 Inhibitory monoclonal antibody to human cytochrome P450 2B6. Biochem Pharmacol. 1998 May 15;55(10):1633-40.
6 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
7 Expression and characterization of human cytochrome P450 4F11: putative role in the metabolism of therapeutic drugs and eicosanoids. Toxicol Appl Pharmacol. 2004 Sep 15;199(3):295-304.
8 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.
9 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
10 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.
11 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
12 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.
13 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.
14 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
15 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.
16 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.
17 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
18 Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
19 CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
20 Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
21 Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
22 Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
23 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
24 Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
25 The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol. 1993 Jan;44(1):61-7.
26 Drug Interactions Flockhart Table
27 Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
28 The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
29 Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
30 Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. Biochem Pharmacol. 1999 Sep 1;58(5):787-96.
31 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
32 Insights into CYP2B6-mediated drug-drug interactions. Acta Pharm Sin B. 2016 Sep;6(5):413-425.
33 Drugs that may have potential CYP2B6 interactions.
34 Involvement of human cytochrome P450 2B6 in the omega- and 4-hydroxylation of the anesthetic agent propofol. Xenobiotica. 2007 Jul;37(7):717-24.
35 Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos. 2005 Dec;33(12):1760-4.
36 PharmGKB summary: phenytoin pathway. Pharmacogenet Genomics. 2012 Jun;22(6):466-70.
37 Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
38 Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
39 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.
40 Clinical pipeline report, company report or official report of signaturerx.
41 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
42 The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
43 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.
44 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
45 Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
46 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.
47 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).