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

General Information of Drug (ID: DMT2CZK)

• Drug Name: Leucine-enkephalin Drug Info
• Synonyms: YGGFL; URLZCHNOLZSCCA-UHFFFAOYSA-N; 2-[[2-[[2-[[2-[[2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid; Spectrum_001429; AC1L1GYW; Spectrum5_000656; Spectrum4_001048; Spectrum2_001177; Spectrum3_001521; AC1Q1P3H; KBioSS_001909; KBioGR_001316; BSPBio_002902

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 461776
  ChEBI ID: CHEBI:89656
  CAS Number: CAS 58822-25-6
  TTD Drug ID: DMT2CZK

Molecule-Related Drug Atlas

Drug(s) Targeting Opioid receptor mu (MOP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Buprenorphine	DMPRI8G	Opioid dependence	6C43.2Z	Approved	[5]
Morphine	DMRMS0L	Advanced cancer	2A00-2F9Z	Approved	[6]
Hydromorphone	DMHP21E	Back pain	ME84.Z	Approved	[7]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[8]
Fentanyl	DM8WAHT	Analgesia	MB40.8	Approved	[9]
Alfentanil	DMVO0UB	Anaesthesia	9A78.6	Approved	[10]
Naloxegol	DML0B41	Opioid-induced constipation	DB32.1	Approved	[11]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[12]
Nalfurafine hcl	DMA9DHW	Uremic pruritus	EC90.10	Approved	[13]
Oxycodone	DMXLKHV	Osteoarthritis	FA00-FA05	Approved	[14]

Drug(s) Targeting Opioid receptor delta (OPRD1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Codeine	DMJX6ZG	Allergic rhinitis	CA08.0	Approved	[15]
Hydromorphone	DMHP21E	Back pain	ME84.Z	Approved	[16]
Loperamide	DMOJZQ9	Diarrhea	ME05.1	Approved	[17]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[12]
Oxycodone	DMXLKHV	Osteoarthritis	FA00-FA05	Approved	[18]
Butorphanol	DM5KYPJ	Pain	MG30-MG3Z	Approved	[15]
Carfentanil	DM7ADGX	N. A.	N. A.	Phase 2	[19]
Met-enkephalin	DMSZFTP	Pain	MG30-MG3Z	Phase 2	[20]
AZD-2327	DM8FZOG	Anxiety disorder	6B00-6B0Z	Phase 2	[21]
ADL-5747	DMMUPTN	Pain	MG30-MG3Z	Phase 2	[22]

Drug(s) Affected By Dipeptidyl peptidase 3 (DPP3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[23]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]
Piroxicam	DMTK234	Osteoarthritis	FA00-FA05	Approved	[26]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[27]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[28]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[29]
(+)-JQ1	DM1CZSJ	Testicular cancer	2C80	Phase 1	[30]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[31]
PMID28460551-Compound-2	DM4DOUB	N. A.	N. A.	Patented	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor delta (OPRD1)	TT27RFC	OPRD_HUMAN	Agonist	[2]
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Dipeptidyl peptidase 3 (DPP3)	OTUIVL1C	DPP3_HUMAN	Biotransformations	[4]

References

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• [2] Inverse agonist action of Leu-enkephalin at delta(2)-opioid receptors mediates spinal antianalgesia. J Pharmacol Exp Ther. 2001 May;297(2):582-9.
• [3] Peptides as receptor selectivity modulators of opiate pharmacophores. J Med Chem. 1986 Jul;29(7):1222-5.
• [4] Identification of dipeptidyl peptidase III in human neutrophils. Biochem Biophys Res Commun. 2000 Jul 5;273(2):393-7. doi: 10.1006/bbrc.2000.2827.
• [5] Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
• [6] 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.
• [7] Clinical pipeline report, company report or official report of signaturerx.
• [8] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [9] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [10] 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.
• [11] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
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• [14] 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).
• [15] Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors. J Pharmacol Sci. 2005 Jun;98(2):109-16.
• [16] Identification of opioid ligands possessing mixed micro agonist/delta antagonist activity among pyridomorphinans derived from naloxone, oxymorphone, and hydromorphone [correction of hydropmorphone]. J Med Chem. 2004 Mar 11;47(6):1400-12.
• [17] Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci. 1983;33 Suppl 1:315-8.
• [18] Oxycodone: a pharmacological and clinical review. Clin Transl Oncol. 2007 May;9(5):298-307.
• [19] Wax PM, Becker CE, Curry SC: Unexpected gas casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5.
• [20] Delta-opioid receptor agonists inhibit neuromuscular transmission in human colon. Eur J Pharmacol. 1994 Sep 1;262(1-2):33-9.
• [21] Preclinical pharmacology of AZD2327: a highly selective agonist of the delta-opioid receptor. J Pharmacol Exp Ther. 2011 Jul;338(1):195-204.
• [22] 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: 317).
• [23] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [24] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [25] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [26] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [27] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [28] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [29] A genomic screen for activators of the antioxidant response element. Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5205-10. doi: 10.1073/pnas.0700898104. Epub 2007 Mar 12.
• [30] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [31] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [32] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.