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

General Information of Drug (ID: DMUPA7C)

• Drug Name: NOCICEPTIN Drug Info
• Synonyms: Nociceptin; Orphanin FQ; Nociceptin/orphanin FQ; 170713-75-4; Orphanin FQ (rat); Orphanin FQ (swine); Orphanin FQ (human); Nociceptin (1-17); UNII-7AYI9N34FF; Orphanin FQ (pig); 7AYI9N34FF; CHEBI:80266; Human nociceptin; L-Glutamine, L-phenylalanylglycylglycyl-L-phenylalanyl-L-threonylglycyl-L-alanyl-L-arginyl-L-lysyl-L-seryl-L-alanyl-L-arginyl-L-lysyl-L-leucyl-L-alanyl-L-asparaginyl-; Nociceptin (human); Nociceptin(1-17)-OH; FGGFTGARKSARKLANQ; Orphaninfq(swine)(9ci); GTPL1681; CHEMBL396460; BDBM50004178; AKOS024458690; nociceptin/orphanin FQ

Indication

Disease Entry	ICD 11	Status	REF
Headache	8A80-8A84	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 16131448
  ChEBI ID: CHEBI:80266
  CAS Number: CAS 170713-75-4
  TTD Drug ID: DMUPA7C

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 Nociceptin receptor (OPRL1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[15]
SER-100	DMDW5ZC	Heart failure	BD10-BD13	Phase 2	[16]
BTRX-246040	DMA9238	Major depressive disorder	6A70.3	Phase 2	[17]
LY-2940094	DMB5L6Q	Major depressive disorder	6A70.3	Phase 2	[18]
JTC-801	DMV3UN4	Pain	MG30-MG3Z	Discontinued in Phase 2	[19]
ND1251	DMMLESX	Depression	6A70-6A7Z	Discontinued in Phase 1	[20]
ATI-17000	DMZJVR5	Irritable bowel syndrome	DD91.0	Preclinical	[21]
4-phenyl-1-(1-phenylbutyl)piperidin-4-ol	DMVCIJB	Discovery agent	N.A.	Investigative	[22]
1-(dio-tolylmethyl)-4-phenylpiperidin-4-ol	DMLYO8P	Discovery agent	N.A.	Investigative	[22]
1-benzhydryl-4-ethoxy-4-phenylpiperidine	DM6PIL2	Discovery agent	N.A.	Investigative	[22]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[25]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[26]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[27]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[28]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[29]
bisphenol A	DM2ZLD7	Discovery agent	N.A.	Investigative	[30]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Nociceptin receptor (OPRL1)	TTNT7K8	OPRX_HUMAN	Inhibitor	[2]
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Nociceptin receptor (OPRL1)	OTSN4PCR	OPRX_HUMAN	Protein Interaction/Cellular Processes	[4]

References

• [1] ClinicalTrials.gov (NCT01404091) A Study of Nociceptin/Orphanin FQ Peptide Receptor Occupancy in Healthy Subjects. U.S. National Institutes of Health.
• [2] Binding and in vitro activities of peptides with high affinity for the nociceptin/orphanin FQ receptor, ORL1. J Pharmacol Exp Ther. 1997 Nov;283(2):735-41.
• [3] Synthesis and pharmacological evaluation of 1,2-dihydrospiro[isoquinoline-4(3H),4'-piperidin]-3-ones as nociceptin receptor agonists. J Med Chem. 2008 Feb 28;51(4):1058-62.
• [4] Structural determinants of opioid and NOP receptor activity in derivatives of buprenorphine. J Med Chem. 2011 Oct 13;54(19):6531-7. doi: 10.1021/jm2003238. Epub 2011 Sep 7.
• [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] Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
• [16] Clinical pipeline report, company report or official report of Serodus ASA.
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs. Biochemical Pharmacology Volume 95, Issue 2, 15 May 2015, Pages 81-97.
• [19] Nociceptin receptor antagonist JTC-801 inhibits nitrous oxide-induced analgesia in mice. J Anesth. 2009;23(2):301-3.
• [20] The nociceptin receptor as a potential target in drug design. Drug News Perspect. 2001 Aug;14(6):335-45.
• [21] Nocistatin and nociceptin given centrally induce opioid-mediated gastric mucosal protection. Peptides. 2008 Dec;29(12):2257-65.
• [22] Bioorg Med Chem Lett. 2007 Jun 1;17(11):3023-7. Epub 2007 Mar 23.Synthesis and structure-activity relationships of 4-hydroxy-4-phenylpiperidines as nociceptin receptor ligands: Part 1.
• [23] ?(9)-Tetrahydrocannabinol decreases NOP receptor density and mRNA levels in human SH-SY5Y cells. J Mol Neurosci. 2012 Feb;46(2):285-92. doi: 10.1007/s12031-011-9552-0. Epub 2011 May 21.
• [24] 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.
• [25] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [26] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [27] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [28] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [29] 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.
• [30] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.