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

General Information of Drug (ID: DMRM0OW)

• Drug Name: DADLE Drug Info
• Synonyms: Dadle; 63631-40-3; H-TYR-D-ALA-GLY-PHE-D-LEU-OH; DADL; (D-Ala2,D-Leu5)-Enkephalin; [D-Ala2, D-Leu5]-enkephalin; CHEMBL340032; BW-180C; Tyr-D-Ala-Gly-Phe-D-Leu; (2R,5S,11R,14S)-14-Amino-5-benzyl-15-(4-hydroxyphenyl)-2-isobutyl-11-methyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazapentadecan-1-oic acid; (2R)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid; UNII-HB4QD9GL6F; HB4QD9GL6F; DADLE-OH; AC1OCEJN; ZINC14952092; H-Tyr-D-Ala-Gly-Phe-D-Leu

Indication

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

• Cross-matching ID:
  PubChem CID: 6917707
  CAS Number: CAS 63631-40-3
  TTD Drug ID: DMRM0OW
  VARIDT Drug ID: DR01490

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) Transported By Organic anion transporting polypeptide 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[4]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[25]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[24]
Pravastatin	DM6A0X7	Adult acute monocytic leukemia		Approved	[26]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[27]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[28]
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[29]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[26]

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 Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[4]

References

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• [2] Delta opioid receptor stimulation mimics ischemic preconditioning in human heart muscle. J Am Coll Cardiol. 2000 Dec;36(7):2296-302.
• [3] Design, synthesis, and biological evaluation of novel bifunctional C-terminal-modified peptides for delta/mu opioid receptor agonists and neurokini... J Med Chem. 2007 Jun 14;50(12):2779-86.
• [4] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [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.
• [12] Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
• [13] 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.
• [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] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [24] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [25] Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
• [26] The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
• [27] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [28] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [29] FDA Drug Development and Drug Interactions