Target Information

Target General Infomation
Target ID
T52921
Former ID
TTDR01247
Target Name
Nociceptin receptor
Gene Name
OPRL1
Synonyms
KOR-3; Kappa-type 3 opioid receptor; OP(4); ORL-1; ORL-1 receptor; Opioid receptor 4; Opioid receptor like-1 receptor; Opioid-receptor-like 1; Orphanin FQ receptor; OPRL1
Target Type
Clinical Trial
Disease Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Central nervous system disease [ICD10: G00-G99]
Headache [ICD9: 339, 784.0; ICD10: G43-G44, R51]
Heart failure [ICD9: 428; ICD10: I50]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Major depressive disorder [ICD9: 296.2, 296.3, 710.0; ICD10: F32, F33, M32]
Pain; Stress [ICD9: 300, 338,780; ICD10: F40-F42, R52, G89]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Psychiatric disorder [ICD9: 290-319; ICD10: F01-F99]
Function
G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.
BioChemical Class
GPCR rhodopsin
Target Validation
T52921
UniProt ID
P41146
Sequence
MEPLFPAPFWEVIYGSHLQGNLSLLSPNHSLLPPHLLLNASHGAFLPLGLKVTIVGLYLA
VCVGGLLGNCLVMYVILRHTKMKTATNIYIFNLALADTLVLLTLPFQGTDILLGFWPFGN
ALCKTVIAIDYYNMFTSTFTLTAMSVDRYVAICHPIRALDVRTSSKAQAVNVAIWALASV
VGVPVAIMGSAQVEDEEIECLVEIPTPQDYWGPVFAICIFLFSFIVPVLVISVCYSLMIR
RLRGVRLLSGSREKDRNLRRITRLVLVVVAVFVGCWTPVQVFVLAQGLGVQPSSETAVAI
LRFCTALGYVNSCLNPILYAFLDENFKACFRKFCCASALRRDVQVSDRVRSIAKDVALAC
KTSETVPRPA
Drugs and Mode of Action
Drug(s) LY-2940094 Drug Info Phase 2 Major depressive disorder [524117]
SER-100 Drug Info Phase 2 Heart failure [521792]
NOCICEPTIN Drug Info Phase 1 Headache [523563]
JTC-801 Drug Info Discontinued in Phase 2 Pain [539047], [547428]
Inhibitor 1-(1,2-diphenylethyl)-4-phenylpiperidin-4-ol Drug Info [528785]
1-(2-ethoxy-1-phenylethyl)-4-phenylpiperidin-4-ol Drug Info [528785]
1-(3,3-diphenylpropyl)-4-phenylpiperidin-4-ol Drug Info [528785]
1-(dio-tolylmethyl)-4-phenylpiperidin-4-ol Drug Info [528785]
1-benzhydryl-4-(2-fluorophenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(2-methoxyphenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(3-fluorophenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(3-methoxyphenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(3-phenylpropyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(4-bromophenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(4-butylphenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(4-chlorophenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(4-ethylphenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(4-fluorophenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(4-methoxyphenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(4-propylphenyl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(benzyloxy)-4-phenylpiperidine Drug Info [528785]
1-benzhydryl-4-(furan-2-yl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(pyridin-2-yl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-(thiophen-2-yl)piperidin-4-ol Drug Info [528781]
1-benzhydryl-4-benzylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-butylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-cyclohexylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-cyclopropylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-ethoxy-4-phenylpiperidine Drug Info [528785]
1-benzhydryl-4-hexylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-isopropylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-m-tolylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-methoxy-4-phenylpiperidine Drug Info [528785]
1-benzhydryl-4-o-tolylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-p-tolylpiperidin-4-ol Drug Info [528781]
1-benzhydryl-4-phenyl-4-propoxypiperidine Drug Info [528785]
1-benzhydryl-4-phenylpiperidin-4-ol Drug Info [530052]
1-benzhydryl-4-tert-butylpiperidin-4-ol Drug Info [528781]
1-benzyl-4-phenylpiperidin-4-ol Drug Info [528785]
2,2-diMeBut-RYYRIK-NH2 Drug Info [529208]
2-MePen-RYYRIK-NH2 Drug Info [529208]
3-(1-benzylpiperidin-4-yl)-5-chloro-1H-indole Drug Info [528151]
4-(2-(aminomethyl)phenyl)-1-benzylpiperidin-4-ol Drug Info [528781]
4-phenyl-1-(1-phenylbutyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(1-phenylethyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(1-phenylheptyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(1-phenylhexyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(1-phenylpentyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(1-phenylpropan-2-yl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(1-phenylpropyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(3-phenylpropyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(phenyl(m-tolyl)methyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(phenyl(o-tolyl)methyl)piperidin-4-ol Drug Info [528785]
4-phenyl-1-(phenyl(p-tolyl)methyl)piperidin-4-ol Drug Info [528785]
Ac-Phe-[Orn-Pro-cha-Trp-Arg] Drug Info [528343]
Ac-RYYRIK-GGG-K-(NH2)-YAFGYPS-GG Drug Info [528282]
Ac-RYYRIK-GGG-K-(NH2)-YRFB-GGGGG Drug Info [528282]
Ac-RYYRIK-K-(NH2)-YAFGYPS Drug Info [528282]
Ac-RYYRIK-K-(NH2)-YRFB Drug Info [528282]
Ac-RYYRIK-NH2 Drug Info [528282]
Ada-RYYRIK-NH2 Drug Info [529208]
Bu-RYYRIK-NH2 Drug Info [529208]
Bz--RYYRIK-NH2 Drug Info [529208]
CFGGFTCARKSARK Drug Info [526185]
CFGGFTGARKCARK Drug Info [526185]
Cyclo-[Asp6,Lys10]N/OFQ(1-13)NH2 Drug Info [529593]
Cyclo[Cys6,Cys10]N/OFQ(1-13)NH2 Drug Info [529593]
Cyclo[Cys7,Cys10]N/OFQ(1-13)NH2 Drug Info [529593]
Cyclo[DAsp7,Lys10]N/OFQ(1-13)NH2 Drug Info [529593]
EtBut-RYYRIK-NH2 Drug Info [529208]
F-G-G-F-T-G-A-R-K-S-A-R-K-L-Aib-N-Q-CONH2 Drug Info [526456]
F-G-G-F-T-G-A-R-K-S-A-R-K-L-Aib-N-Q-COOH Drug Info [526456]
F-G-G-F-T-G-A-R-K-S-A-R-K-L-MeA-N-Q-CONH2 Drug Info [526456]
F-G-G-F-T-G-A-R-K-S-A-R-K-L-MeA-N-Q-COOH Drug Info [526456]
F-G-G-F-T-G-A-R-K-S-Aib-R-K-L-A-N-Q-CONH2 Drug Info [526456]
F-G-G-F-T-G-A-R-K-S-Aib-R-K-L-A-N-Q-COOH Drug Info [526456]
F-G-G-F-T-G-A-R-K-S-MeA-R-K-L-A-N-Q-CONH2 Drug Info [526456]
F-G-G-F-T-G-A-R-K-S-MeA-R-K-L-A-N-Q-COOH Drug Info [526456]
F-G-G-F-T-G-Aib-R-K-S-A-R-K-L-A-N-Q-CONH2 Drug Info [526456]
F-G-G-F-T-G-Aib-R-K-S-A-R-K-L-A-N-Q-COOH Drug Info [526456]
F-G-G-F-T-G-Aib-R-K-S-Aib-R-K-L-A-N-Q-CONH2 Drug Info [526456]
F-G-G-F-T-G-MeA-R-K-S-A-R-K-L-A-N-Q-CONH2 Drug Info [526456]
F-G-G-F-T-G-MeA-R-K-S-A-R-K-L-A-N-Q-COOH Drug Info [526456]
FGGFTCARKCARK Drug Info [526185]
FGGFTGARKCARKC Drug Info [526185]
FGGFTGARKRKRKLANQ Drug Info [529719]
FGGFTGARKSARK Drug Info [526185]
FGGFTGARKSARKAANQ Drug Info [529719]
FGGFTGARKSARKFANQ Drug Info [529719]
FGGFTGARKSARKKANQ Drug Info [529719]
FGGFTGARKSARKKKNQ Drug Info [529719]
FGGFTGARKSARKKRNQ Drug Info [529719]
FGGFTGARKSARKKWNQ Drug Info [530249]
FGGFTGARKSARKL Drug Info [526185]
FGGFTGARKSARKLADE Drug Info [526185]
FGGFTGARKSARKLARK Drug Info [529719]
FGGFTGARKSARKLFNQ Drug Info [529719]
FGGFTGARKSARKLKNQ Drug Info [529719]
FGGFTGARKSARKLLNQ Drug Info [529719]
FGGFTGARKSARKLRNQ Drug Info [529719]
FGGFTGARKSARKLVNQ Drug Info [529719]
FGGFTGARKSARKLWNQ Drug Info [530249]
FGGFTGARKSARKLYNQ Drug Info [529719]
FGGFTGARKSARKRANQ Drug Info [529719]
FGGFTGARKSARKRKNQ Drug Info [530249]
FGGFTGARKSARKRKRK Drug Info [529719]
FGGFTGARKSARKRRNQ Drug Info [529719]
FGGFTGARKSARKRWNQ Drug Info [530249]
FGGFTGARKSARKVANQ Drug Info [529719]
FGGFTGARKSARKWANQ Drug Info [530249]
FGGFTGARKSARKWKNQ Drug Info [530249]
FGGFTGARKSARKWRNQ Drug Info [530249]
FGGFTGARKSARKYANQ Drug Info [529719]
FGGFTGCRKSARKC Drug Info [526185]
FGGFTGCRKSCRK Drug Info [526185]
FGGFTRKRKSARKLANQ Drug Info [529719]
FLUPERAMIDE Drug Info [527228]
For-RYYRIK-NH2 Drug Info [529208]
H-RYYRIK-NH2 Drug Info [529208]
Hex-RYYRIK-NH2 Drug Info [529208]
IsoBu-RYYRIK-NH2 Drug Info [529208]
IsoVa-RYYRIK-NH2 Drug Info [529208]
MeBut-RYYRIK-NH2 Drug Info [529208]
NOCICEPTIN Drug Info [529719]
Piv-RYYRIK-NH2 Drug Info [529208]
Pr-RYYRIK-NH2 Drug Info [529208]
T-BuAc-RYYRIK-NH2 Drug Info [529208]
Va-RYYRIK-NH2 Drug Info [529208]
[Asp6,Lys10]N/OFQ(1-13)NH2 Drug Info [529593]
[D-Asp7,Lys10]N/OFQ(1-13)NH2 Drug Info [529593]
Antagonist Banyu Compound-24 Drug Info [530141]
BND-001 Drug Info [543766]
J-113397 Drug Info [535360], [535745], [536893]
JTC-801 Drug Info [537331]
peptide III-BTD Drug Info [525587]
PF-454583 Drug Info [543766]
SB-612111 Drug Info [543766]
UFP-101 Drug Info [526331]
[Nphe(1)]-nociceptin (1-13)-NH(2) Drug Info [535360]
Modulator LY-2940094 Drug Info [551571], [551633]
Agonist N/OFQ-(1-13)-NH2 Drug Info [534406]
nociceptin/orphanin FQ Drug Info [534499]
Ro-64-6198 Drug Info [535745]
SCH-221510 Drug Info [543766]
SER-100 Drug Info [551680]
Syn-1020 Drug Info [543766]
UFP-112 Drug Info [529945]
Binder Nociceptin/orphanin FQ receptor PET ligands Drug Info [543766]
SR-14136 Drug Info [543766]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
PANTHER Pathway Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
Reactome Peptide ligand-binding receptors
G alpha (i) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
References
Ref 521792ClinicalTrials.gov (NCT00283361) ZP120 Add-on to Furosemide in Treatment of Acute or Sub-Acute Decompensated Heart Failure. U.S. National Institutes of Health.
Ref 523563ClinicalTrials.gov (NCT01404091) A Study of Nociceptin/Orphanin FQ Peptide Receptor Occupancy in Healthy Subjects. U.S. National Institutes of Health.
Ref 524117ClinicalTrials.gov (NCT01724112) Study of the Efficacy and Safety of LY2940094 in Participants With Major Depressive Disorder (MDD). U.S. National Institutes of Health.
Ref 539047(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. (Ligand id: 1692).
Ref 547428Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016171)
Ref 525587Ligands for kappa-opioid and ORL1 receptors identified from a conformationally constrained peptide combinatorial library. J Biol Chem. 1999 Sep 24;274(39):27513-22.
Ref 526185J Med Chem. 2001 Nov 8;44(23):4015-8.Structure-activity studies on nociceptin analogues: ORL1 receptor binding and biological activity of cyclic disulfide-containing analogues of nociceptin peptides.
Ref 526331Nphe1,Arg14,Lys15nociceptin-NH2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor. Br J Pharmacol. 2002 May;136(2):303-11.
Ref 526456J Med Chem. 2002 Nov 21;45(24):5280-6.Novel, potent ORL-1 receptor agonist peptides containing alpha-Helix-promoting conformational constraints.
Ref 527228Bioorg Med Chem Lett. 2004 Nov 1;14(21):5275-9.Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor.
Ref 528151Bioorg Med Chem Lett. 2006 Jul 1;16(13):3524-8. Epub 2006 Apr 24.3-(4-Piperidinyl)indoles and 3-(4-piperidinyl)pyrrolo-[2,3-b]pyridines as ligands for the ORL-1 receptor.
Ref 528282Bioorg Med Chem Lett. 2006 Sep 15;16(18):4839-41. Epub 2006 Jun 30.Synthesis and receptor binding properties of chimeric peptides containing a mu-opioid receptor ligand and nociceptin/orphanin FQ receptor ligand Ac-RYYRIK-amide.
Ref 528343Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92. Epub 2006 Jul 28.Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivoactivity.
Ref 528781Bioorg Med Chem Lett. 2007 Jun 1;17(11):3028-33. Epub 2007 Mar 21.Synthesis and structure-activity relationships of 4-hydroxy-4-phenylpiperidines as nociceptin receptor ligands: Part 2.
Ref 528785Bioorg 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.
Ref 529208Bioorg Med Chem. 2008 Mar 1;16(5):2635-44. Epub 2007 Nov 21.Designed modification of partial agonist of ORL1 nociceptin receptor for conversion into highly potent antagonist.
Ref 529593J Med Chem. 2008 Aug 14;51(15):4385-7. Epub 2008 Jul 15.High affinity conformationally constrained nociceptin/orphanin FQ(1-13) amide analogues.
Ref 529719Bioorg Med Chem. 2008 Oct 15;16(20):9261-7. Epub 2008 Sep 9.Synergistic effect of basic residues at positions 14-15 of nociceptin on binding affinity and receptor activation.
Ref 529945Pharmacological profile of NOP receptors coupled with calcium signaling via the chimeric protein G alpha qi5. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jun;379(6):599-607.
Ref 530052Bioorg Med Chem Lett. 2009 May 1;19(9):2519-23. Epub 2009 Mar 14.The discovery of tropane derivatives as nociceptin receptor ligands for the management of cough and anxiety.
Ref 530141Pharmacological characterization of the nociceptin/orphanin FQ receptor non peptide antagonist Compound 24. Eur J Pharmacol. 2009 Jul 1;614(1-3):50-7.
Ref 530249Bioorg Med Chem. 2009 Aug 1;17(15):5683-7. Epub 2009 Jun 13.Discriminatory synergistic effect of Trp-substitutions in superagonist [(Arg/Lys)(14), (Arg/Lys)(15)]nociceptin on ORL1 receptor binding and activation.
Ref 534406Address and message sequences for the nociceptin receptor: a structure-activity study of nociceptin-(1-13)-peptide amide. J Med Chem. 1997 Jun 6;40(12):1789-93.
Ref 534499Binding 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.
Ref 535360Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test. Naunyn Schmiedebergs Arch Pharmacol. 2002 Feb;365(2):164-7. Epub 2001 Dec 20.
Ref 535745The nociceptin receptor as a potential target in drug design. Drug News Perspect. 2001 Aug;14(6):335-45.
Ref 536574Therapeutic applications of aptamers. Expert Opin Investig Drugs. 2008 Jan;17(1):43-60.
Ref 536893Nocistatin and nociceptin given centrally induce opioid-mediated gastric mucosal protection. Peptides. 2008 Dec;29(12):2257-65. Epub 2008 Sep 26.
Ref 537331Nociceptin receptor antagonist JTC-801 inhibits nitrous oxide-induced analgesia in mice. J Anesth. 2009;23(2):301-3. Epub 2009 May 15.
Ref 543766(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: 320).
Ref 551571UK Journal of Pharmaceutical and Biosciences Vol. 3(1), 12-17, 2015.
Ref 551633Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs. Biochemical Pharmacology Volume 95, Issue 2, 15 May 2015, Pages 81-97.
Ref 551680Clinical pipeline report, company report or official report of Serodus ASA.

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