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Identification
- Summary
Metenkefalin is an investigational endogenous opioid being studied for the treatment of COVID-19.
- Generic Name
- Metenkefalin
- DrugBank Accession Number
- DB12668
- Background
Metenkefalin is an endogenous opioid and beta-endorphin.2 It has been shown to reduce chromosomal abberations in patients with multiple sclerosis.1 Metenkefalin, along with tridecactide, are under investigation as an immunomodulatory therapy for moderate to severe COVID-19.5,6
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Metenkefalin (DB12668)
- Weight
- Average: 573.67
Monoisotopic: 573.225719661 - Chemical Formula
- C27H35N5O7S
- Synonyms
- [met5]-enkephalin
- Metenkefalin
- Methionine Enkephalin
- External IDs
- INNO-105
Pharmacology
- Indication
Metenkefalin is indicated in Bosnia for the treatment of relapsing-remitting multiple sclerosis.7
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
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Not Available
- Mechanism of action
Metenkefalin is an agonist of µ and δ opioid receptors.3 It also causes immunostimulation at low doses and immunosuppression at higher doses.3 Metenkefalin can also inhibit the production of aldosterone, deoxycorticosterone, and corticosterone.4 Unfortunately, the mechanisms by which these effects occur have not been well described in the literature.
Target Actions Organism ADelta-type opioid receptor agonistHumans UMu-type opioid receptor agonistHumans - Absorption
Metenkefalin reaches a Cmax of 1266.14pg/mL, with a Tmax of 0.16h, and an AUC of 360.64pg*h/mL.7
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
The half life of metenkefalin is 4.2-39 minutes.7
- Clearance
Not Available
- Adverse Effects
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Data regarding overdoses of metenkefalin are not readily available.7 Animal overdose studies have not determined an LD50.7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Metenkefalin acetate RBM01752JM 82362-17-2 Not applicable
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Oligopeptides
- Alternative Parents
- Tyrosine and derivatives / Phenylalanine and derivatives / Methionine and derivatives / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Amphetamines and derivatives / Thia fatty acids / Hydroxy fatty acids / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids show 12 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-oligopeptide / Amine / Amino acid / Amino acid or derivatives / Amphetamine or derivatives / Aralkylamine / Aromatic homomonocyclic compound show 32 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- peptide (CHEBI:6618)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 9JEZ9OD3AS
- CAS number
- 58569-55-4
- InChI Key
- YFGBQHOOROIVKG-FKBYEOEOSA-N
- InChI
- InChI=1S/C27H35N5O7S/c1-40-12-11-21(27(38)39)32-26(37)22(14-17-5-3-2-4-6-17)31-24(35)16-29-23(34)15-30-25(36)20(28)13-18-7-9-19(33)10-8-18/h2-10,20-22,33H,11-16,28H2,1H3,(H,29,34)(H,30,36)(H,31,35)(H,32,37)(H,38,39)/t20-,21-,22-/m0/s1
- IUPAC Name
- (2S)-2-[(2S)-2-(2-{2-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]acetamido}acetamido)-3-phenylpropanamido]-4-(methylsulfanyl)butanoic acid
- SMILES
- CSCC[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1)C(O)=O
References
- General References
- Rakanovic-Todic M, Ibrulj S, Brunazovic-Ristic L, Catovic A, Aganovic-Musinovic I, Kusturica J: Cytogenetic effects of combination of tridecactide and met-enkephalin on lymphocytes of patients with multiple sclerosis Journal of Health Sciences. 2014 Apr 6;5(1):5-10. [Article]
- Zoccali C: Elimination of plasma metenkephalin. Nephrol Dial Transplant. 1989;4(3):236. doi: 10.1093/oxfordjournals.ndt.a091862. [Article]
- Rakanovic-Todic M, Burnazovic-Ristic L, Ibrulj S, Mulbegovic N: Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis. Bosn J Basic Med Sci. 2014 May;14(2):75-80. doi: 10.17305/bjbms.2014.2267. [Article]
- Racz K, Varga I, Glaz E, Kiss R, Vida S, Lada G, di Gleria K, Medzihradszky K, Lichtwald K, Vecsei P: Met-enkephalin inhibits mineralocorticoid production in isolated human aldosteronoma cells. J Clin Endocrinol Metab. 1982 Mar;54(3):656-60. doi: 10.1210/jcem-54-3-656. [Article]
- NIH: Clinical Trial to Evaluate the Efficacy and Safety of an Immunomodulatory Therapy for the Treatment of Patients With Moderate to Severe COVID-19 Infection (NCT04374032) [Link]
- Bosna Lijek: Enkorten Metenkefalin and Tridecactide Injection [Link]
- Bosna Lijek: Enkorten Summary of Product Characteristics [Link]
- External Links
- KEGG Compound
- C11684
- PubChem Compound
- 443363
- PubChem Substance
- 347828872
- ChemSpider
- 391597
- BindingDB
- 50019056
- 1349278
- ChEBI
- 189868
- ChEMBL
- CHEMBL13786
- ZINC
- ZINC000004102171
- Wikipedia
- Met-enkephalin
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2, 3 Completed Treatment Coronavirus Disease 2019 (COVID‑19) / Covid 19 Infection 1 somestatus stop reason just information to hide 1 Completed Treatment Liver Cancer 1 somestatus stop reason just information to hide 1 Terminated Treatment Tumor 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0196 mg/mL ALOGPS logP 0.28 ALOGPS logP -2.5 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 3.61 Chemaxon pKa (Strongest Basic) 7.73 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 7 Chemaxon Polar Surface Area 199.95 Å2 Chemaxon Rotatable Bond Count 16 Chemaxon Refractivity 149.01 m3·mol-1 Chemaxon Polarizability 58.85 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 249.3977708 predictedDarkChem Lite v0.1.0 [M-H]- 220.88329 predictedDeepCCS 1.0 (2019) [M+H]+ 249.0619708 predictedDarkChem Lite v0.1.0 [M+H]+ 222.73257 predictedDeepCCS 1.0 (2019) [M+Na]+ 250.6795708 predictedDarkChem Lite v0.1.0 [M+Na]+ 228.5085 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine
- Specific Function
- G protein-coupled enkephalin receptor activity
- Gene Name
- OPRD1
- Uniprot ID
- P41143
- Uniprot Name
- Delta-type opioid receptor
- Molecular Weight
- 40368.235 Da
References
- Rakanovic-Todic M, Burnazovic-Ristic L, Ibrulj S, Mulbegovic N: Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis. Bosn J Basic Med Sci. 2014 May;14(2):75-80. doi: 10.17305/bjbms.2014.2267. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity)
- Specific Function
- beta-endorphin receptor activity
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Rakanovic-Todic M, Burnazovic-Ristic L, Ibrulj S, Mulbegovic N: Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis. Bosn J Basic Med Sci. 2014 May;14(2):75-80. doi: 10.17305/bjbms.2014.2267. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- May be involved in the proteolytic inactivation of enkephalins and neurotensin in some brain areas. May convert inactive angiotensin I into the biologically active angiotensin II (PubMed:18178555). Releases a C-terminal amino acid, with preference for large hydrophobic C-terminal amino acids and shows only very weak activity toward small amino acids and histidine (PubMed:20855895)
- Specific Function
- metallocarboxypeptidase activity
- Gene Name
- CPA6
- Uniprot ID
- Q8N4T0
- Uniprot Name
- Carboxypeptidase A6
- Molecular Weight
- 51007.48 Da
References
- Lyons PJ, Callaway MB, Fricker LD: Characterization of carboxypeptidase A6, an extracellular matrix peptidase. J Biol Chem. 2008 Mar 14;283(11):7054-63. doi: 10.1074/jbc.M707680200. Epub 2008 Jan 4. [Article]
Drug created at October 20, 2016 23:33 / Updated at August 26, 2024 19:23