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

General Information of Drug (ID: DMZN93Y)

• Drug Name: MCL-458 Drug Info
• Synonyms: MCL-458; CHEMBL390912; BDBM50210556

Indication

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

• Cross-matching ID:
  PubChem CID: 44429061
  TTD Drug ID: DMZN93Y

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	[2]
Morphine	DMRMS0L	Advanced cancer	2A00-2F9Z	Approved	[3]
Hydromorphone	DMHP21E	Back pain	ME84.Z	Approved	[4]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[5]
Fentanyl	DM8WAHT	Analgesia	MB40.8	Approved	[6]
Alfentanil	DMVO0UB	Anaesthesia	9A78.6	Approved	[7]
Naloxegol	DML0B41	Opioid-induced constipation	DB32.1	Approved	[8]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[9]
Nalfurafine hcl	DMA9DHW	Uremic pruritus	EC90.10	Approved	[10]
Oxycodone	DMXLKHV	Osteoarthritis	FA00-FA05	Approved	[11]

Drug(s) Targeting Opioid receptor delta (OPRD1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Codeine	DMJX6ZG	Allergic rhinitis	CA08.0	Approved	[12]
Hydromorphone	DMHP21E	Back pain	ME84.Z	Approved	[13]
Loperamide	DMOJZQ9	Diarrhea	ME05.1	Approved	[14]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[9]
Oxycodone	DMXLKHV	Osteoarthritis	FA00-FA05	Approved	[15]
Butorphanol	DM5KYPJ	Pain	MG30-MG3Z	Approved	[12]
Carfentanil	DM7ADGX	N. A.	N. A.	Phase 2	[16]
Met-enkephalin	DMSZFTP	Pain	MG30-MG3Z	Phase 2	[17]
AZD-2327	DM8FZOG	Anxiety disorder	6B00-6B0Z	Phase 2	[18]
ADL-5747	DMMUPTN	Pain	MG30-MG3Z	Phase 2	[19]

Drug(s) Targeting Opioid receptor kappa (OPRK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nalbuphine	DMOSQGU	Pain	MG30-MG3Z	Approved	[20]
Nalfurafine hcl	DMA9DHW	Uremic pruritus	EC90.10	Approved	[10]
CHLOROXINE	DMFZBMQ	Erythema	ME64.0	Approved	[21]
Difelikefalin	DMHZBEO	Pruritus	EC90	Approved	[22]
Dezocine	DMJDB0Y	Pain	MG30-MG3Z	Approved	[23]
Asimadoline	DMND3AB	Diarrhea-predominant irritable bowel syndrome	DD91.01	Phase 3	[24]
JNJ 67953964	DMJ8Y5N	Major depressive disorder	6A70.3	Phase 3	[25]
PHN-131	DM1SV8I	Pain	MG30-MG3Z	Phase 2/3	[26]
CR-845	DMJYTUQ	Pain	MG30-MG3Z	Phase 2/3	[27]
Carfentanil	DM7ADGX	N. A.	N. A.	Phase 2	[16]

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	Inhibitor	[1]
Opioid receptor kappa (OPRK1)	TTQW87Y	OPRK_HUMAN	Inhibitor	[1]
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Inhibitor	[1]

References

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• [2] Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
• [3] 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.
• [4] Clinical pipeline report, company report or official report of signaturerx.
• [5] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [6] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [7] 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.
• [8] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [9] Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
• [10] 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.
• [11] 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).
• [12] Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors. J Pharmacol Sci. 2005 Jun;98(2):109-16.
• [13] 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.
• [14] Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci. 1983;33 Suppl 1:315-8.
• [15] Oxycodone: a pharmacological and clinical review. Clin Transl Oncol. 2007 May;9(5):298-307.
• [16] Wax PM, Becker CE, Curry SC: Unexpected gas casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5.
• [17] Delta-opioid receptor agonists inhibit neuromuscular transmission in human colon. Eur J Pharmacol. 1994 Sep 1;262(1-2):33-9.
• [18] Preclinical pharmacology of AZD2327: a highly selective agonist of the delta-opioid receptor. J Pharmacol Exp Ther. 2011 Jul;338(1):195-204.
• [19] 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).
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [21] In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
• [22] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [23] Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3.
• [24] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [25] Kappa Opioid Receptor Antagonists as Potential Therapeutics for Mood and Substance Use Disorders. Handb Exp Pharmacol. 2022;271:473-491.
• [26] Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988 Jan;244(1):391-402.
• [27] Peptide Kappa Opioid Receptor Ligands: Potential for Drug Development. AAPS J. 2009 June; 11(2): 312-322.