Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNT7K8)

• DTT Name: Nociceptin receptor (OPRL1)
• Synonyms: Orphanin FQ receptor; Opioid-receptor-like 1; Opioid receptor like-1 receptor; Opioid receptor 4; ORL-1 receptor; ORL-1; OPRL1; OP(4); Kappa-type 3 opioid receptor; KOR-3
• Gene Name: OPRL1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: OPRX_HUMAN
• TTD ID: T52921
• Sequence:
  MEPLFPAPFWEVIYGSHLQGNLSLLSPNHSLLPPHLLLNASHGAFLPLGLKVTIVGLYLA
  VCVGGLLGNCLVMYVILRHTKMKTATNIYIFNLALADTLVLLTLPFQGTDILLGFWPFGN
  ALCKTVIAIDYYNMFTSTFTLTAMSVDRYVAICHPIRALDVRTSSKAQAVNVAIWALASV
  VGVPVAIMGSAQVEDEEIECLVEIPTPQDYWGPVFAICIFLFSFIVPVLVISVCYSLMIR
  RLRGVRLLSGSREKDRNLRRITRLVLVVVAVFVGCWTPVQVFVLAQGLGVQPSSETAVAI
  LRFCTALGYVNSCLNPILYAFLDENFKACFRKFCCASALRRDVQVSDRVRSIAKDVALAC
  KTSETVPRPA
• 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.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BTRX-246040	DMA9238	Major depressive disorder	6A70.3	Phase 2	[2]
LY-2940094	DMB5L6Q	Major depressive disorder	6A70.3	Phase 2	[1]
PMX-53	DMZUAJ4	Atopic dermatitis	EA80	Phase 2	[3]
SER-100	DMDW5ZC	Heart failure	BD10-BD13	Phase 2	[4]
NOCICEPTIN	DMUPA7C	Headache	8A80-8A84	Phase 1	[5]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JTC-801	DMV3UN4	Pain	MG30-MG3Z	Discontinued in Phase 2	[6]
ND1251	DMMLESX	Depression	6A70-6A7Z	Discontinued in Phase 1	[7]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ATI-17000	DMZJVR5	Irritable bowel syndrome	DD91.0	Preclinical	[8]

137 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-(1,2-diphenylethyl)-4-phenylpiperidin-4-ol	DMOR9EK	Discovery agent	N.A.	Investigative	[9]
1-(2-ethoxy-1-phenylethyl)-4-phenylpiperidin-4-ol	DMV3FSH	Discovery agent	N.A.	Investigative	[9]
1-(3,3-diphenylpropyl)-4-phenylpiperidin-4-ol	DMJDK7Z	Discovery agent	N.A.	Investigative	[9]
1-(dio-tolylmethyl)-4-phenylpiperidin-4-ol	DMLYO8P	Discovery agent	N.A.	Investigative	[9]
1-benzhydryl-4-(2-fluorophenyl)piperidin-4-ol	DMTANPG	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(2-methoxyphenyl)piperidin-4-ol	DMWHMNY	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(3-fluorophenyl)piperidin-4-ol	DMXZFPB	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(3-methoxyphenyl)piperidin-4-ol	DM1QYS8	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(3-phenylpropyl)piperidin-4-ol	DMIT7SH	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(4-bromophenyl)piperidin-4-ol	DM0BQYX	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(4-butylphenyl)piperidin-4-ol	DMMAJW9	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(4-chlorophenyl)piperidin-4-ol	DMWYG8K	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(4-ethylphenyl)piperidin-4-ol	DME0BJD	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(4-fluorophenyl)piperidin-4-ol	DMRNZD6	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(4-methoxyphenyl)piperidin-4-ol	DMXT894	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(4-propylphenyl)piperidin-4-ol	DMJDUM5	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(benzyloxy)-4-phenylpiperidine	DMDRUBL	Discovery agent	N.A.	Investigative	[9]
1-benzhydryl-4-(furan-2-yl)piperidin-4-ol	DMMB2GV	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(pyridin-2-yl)piperidin-4-ol	DMJ8F60	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-(thiophen-2-yl)piperidin-4-ol	DMNOZR2	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-benzylpiperidin-4-ol	DMVBR36	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-butylpiperidin-4-ol	DMRN7SC	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-cyclohexylpiperidin-4-ol	DMZVSYD	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-cyclopropylpiperidin-4-ol	DMM94Y2	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-ethoxy-4-phenylpiperidine	DM6PIL2	Discovery agent	N.A.	Investigative	[9]
1-benzhydryl-4-hexylpiperidin-4-ol	DMUK95S	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-isopropylpiperidin-4-ol	DMGYCQ3	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-m-tolylpiperidin-4-ol	DMVJH1S	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-methoxy-4-phenylpiperidine	DMBG0N8	Discovery agent	N.A.	Investigative	[9]
1-benzhydryl-4-o-tolylpiperidin-4-ol	DMVUMSF	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-p-tolylpiperidin-4-ol	DM679RC	Discovery agent	N.A.	Investigative	[10]
1-benzhydryl-4-phenyl-4-propoxypiperidine	DMEB968	Discovery agent	N.A.	Investigative	[9]
1-benzhydryl-4-phenylpiperidin-4-ol	DM7KU1X	Discovery agent	N.A.	Investigative	[11]
1-benzhydryl-4-tert-butylpiperidin-4-ol	DMM5DTF	Discovery agent	N.A.	Investigative	[10]
1-benzyl-4-phenylpiperidin-4-ol	DMNTELW	Discovery agent	N.A.	Investigative	[9]
2,2-diMeBut-RYYRIK-NH2	DMPX642	Discovery agent	N.A.	Investigative	[12]
2-MePen-RYYRIK-NH2	DMDZTU3	Discovery agent	N.A.	Investigative	[12]
3-(1-benzylpiperidin-4-yl)-5-chloro-1H-indole	DM2YKHI	Discovery agent	N.A.	Investigative	[13]
4-(2-(aminomethyl)phenyl)-1-benzylpiperidin-4-ol	DMUYPMO	Discovery agent	N.A.	Investigative	[10]
4-phenyl-1-(1-phenylbutyl)piperidin-4-ol	DMVCIJB	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(1-phenylethyl)piperidin-4-ol	DM6EFLV	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(1-phenylheptyl)piperidin-4-ol	DMISTXQ	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(1-phenylhexyl)piperidin-4-ol	DM1GRWY	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(1-phenylpentyl)piperidin-4-ol	DMZQ7DP	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(1-phenylpropan-2-yl)piperidin-4-ol	DM491FJ	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(1-phenylpropyl)piperidin-4-ol	DMALIQ8	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(3-phenylpropyl)piperidin-4-ol	DMM8O1X	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(phenyl(m-tolyl)methyl)piperidin-4-ol	DMFV0JC	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(phenyl(o-tolyl)methyl)piperidin-4-ol	DM2MPWC	Discovery agent	N.A.	Investigative	[9]
4-phenyl-1-(phenyl(p-tolyl)methyl)piperidin-4-ol	DM5R6T4	Discovery agent	N.A.	Investigative	[9]
Ac-RYYRIK-GGG-K-(NH2)-YAFGYPS-GG	DM512OP	Discovery agent	N.A.	Investigative	[14]
Ac-RYYRIK-GGG-K-(NH2)-YRFB-GGGGG	DMAHQIV	Discovery agent	N.A.	Investigative	[14]
Ac-RYYRIK-K-(NH2)-YAFGYPS	DM2ND3U	Discovery agent	N.A.	Investigative	[14]
Ac-RYYRIK-K-(NH2)-YRFB	DMNA3F4	Discovery agent	N.A.	Investigative	[14]
Ac-RYYRIK-NH2	DMI87UE	Discovery agent	N.A.	Investigative	[14]
Ada-RYYRIK-NH2	DM1MAVU	Discovery agent	N.A.	Investigative	[12]
Banyu Compound-24	DMD26XN	Discovery agent	N.A.	Investigative	[15]
BND-001	DMJI1EA	Central nervous system disease	8A04-8D87	Investigative	[16]
Bu-RYYRIK-NH2	DMDC7MT	Discovery agent	N.A.	Investigative	[12]
Bz--RYYRIK-NH2	DMUW87A	Discovery agent	N.A.	Investigative	[12]
CFGGFTCARKSARK	DMSL4FQ	Discovery agent	N.A.	Investigative	[17]
CFGGFTGARKCARK	DM2B0RX	Discovery agent	N.A.	Investigative	[17]
Cyclo-[Asp6,Lys10]N/OFQ(1-13)NH2	DMWD5RK	Discovery agent	N.A.	Investigative	[18]
Cyclo[Cys6,Cys10]N/OFQ(1-13)NH2	DMSMH6T	Discovery agent	N.A.	Investigative	[18]
Cyclo[Cys7,Cys10]N/OFQ(1-13)NH2	DMI9C57	Discovery agent	N.A.	Investigative	[18]
Cyclo[DAsp7,Lys10]N/OFQ(1-13)NH2	DM39UMT	Discovery agent	N.A.	Investigative	[18]
EtBut-RYYRIK-NH2	DM0IYLS	Discovery agent	N.A.	Investigative	[12]
F-G-G-F-T-G-A-R-K-S-A-R-K-L-Aib-N-Q-CONH2	DMKLSBN	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-A-R-K-S-A-R-K-L-Aib-N-Q-COOH	DMPDMFA	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-A-R-K-S-A-R-K-L-MeA-N-Q-CONH2	DMD9SOF	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-A-R-K-S-A-R-K-L-MeA-N-Q-COOH	DMCSN9M	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-A-R-K-S-Aib-R-K-L-A-N-Q-CONH2	DM9H80P	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-A-R-K-S-Aib-R-K-L-A-N-Q-COOH	DMPRZ8N	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-A-R-K-S-MeA-R-K-L-A-N-Q-CONH2	DMV3ZF1	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-A-R-K-S-MeA-R-K-L-A-N-Q-COOH	DMZI6RD	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-Aib-R-K-S-A-R-K-L-A-N-Q-CONH2	DMN7501	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-Aib-R-K-S-A-R-K-L-A-N-Q-COOH	DMU3IJL	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-Aib-R-K-S-Aib-R-K-L-A-N-Q-CONH2	DMMV061	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-MeA-R-K-S-A-R-K-L-A-N-Q-CONH2	DMPHIBZ	Discovery agent	N.A.	Investigative	[19]
F-G-G-F-T-G-MeA-R-K-S-A-R-K-L-A-N-Q-COOH	DMXH2D8	Discovery agent	N.A.	Investigative	[19]
FGGFTCARKCARK	DML9IGY	Discovery agent	N.A.	Investigative	[17]
FGGFTGARKCARKC	DMTEO35	Discovery agent	N.A.	Investigative	[17]
FGGFTGARKRKRKLANQ	DMIFKPE	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKAANQ	DM5W1VF	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKFANQ	DMYJTZ7	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKKANQ	DMHG2TB	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKKKNQ	DMY347Q	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKKRNQ	DMPG8NC	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKKWNQ	DMHD6N7	Discovery agent	N.A.	Investigative	[21]
FGGFTGARKSARKL	DM78I2W	Discovery agent	N.A.	Investigative	[17]
FGGFTGARKSARKLADE	DMS5AH4	Discovery agent	N.A.	Investigative	[17]
FGGFTGARKSARKLARK	DMSMK70	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKLFNQ	DMLDWFE	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKLKNQ	DMIA2XJ	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKLLNQ	DMRVSXG	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKLRNQ	DMCSTP5	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKLVNQ	DMDEJS6	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKLWNQ	DMV34KQ	Discovery agent	N.A.	Investigative	[21]
FGGFTGARKSARKLYNQ	DMG5LXT	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKRANQ	DM21XBO	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKRKNQ	DM9RHXC	Discovery agent	N.A.	Investigative	[21]
FGGFTGARKSARKRKRK	DMWK0Z6	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKRRNQ	DMDMT5U	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKRWNQ	DMEGW7F	Discovery agent	N.A.	Investigative	[21]
FGGFTGARKSARKVANQ	DM1QTN5	Discovery agent	N.A.	Investigative	[20]
FGGFTGARKSARKWANQ	DMM17AO	Discovery agent	N.A.	Investigative	[21]
FGGFTGARKSARKWKNQ	DM1YN0F	Discovery agent	N.A.	Investigative	[21]
FGGFTGARKSARKWRNQ	DMRLZKJ	Discovery agent	N.A.	Investigative	[21]
FGGFTGARKSARKYANQ	DM5FRXN	Discovery agent	N.A.	Investigative	[20]
FGGFTGCRKSARKC	DM2PYE7	Discovery agent	N.A.	Investigative	[17]
FGGFTGCRKSCRK	DMQX2GK	Discovery agent	N.A.	Investigative	[17]
FGGFTRKRKSARKLANQ	DMD9UQN	Discovery agent	N.A.	Investigative	[20]
FLUPERAMIDE	DMEGL84	Discovery agent	N.A.	Investigative	[22]
For-RYYRIK-NH2	DMVBGAT	Discovery agent	N.A.	Investigative	[12]
H-RYYRIK-NH2	DMSTV96	Discovery agent	N.A.	Investigative	[12]
Hex-RYYRIK-NH2	DMHTWN9	Discovery agent	N.A.	Investigative	[12]
IsoBu-RYYRIK-NH2	DMV8OCF	Discovery agent	N.A.	Investigative	[12]
IsoVa-RYYRIK-NH2	DMNL0BK	Discovery agent	N.A.	Investigative	[12]
MeBut-RYYRIK-NH2	DMYQOKX	Discovery agent	N.A.	Investigative	[12]
N/OFQ-(1-13)-NH2	DMCGVAB	Discovery agent	N.A.	Investigative	[23]
NOX 2137a/b	DMAM5ZO	Pain	MG30-MG3Z	Investigative	[24]
NOX 2149	DMZVDLS	Pain	MG30-MG3Z	Investigative	[24]
peptide III-BTD	DMSDFOC	Discovery agent	N.A.	Investigative	[25]
PF-454583	DMMNEJB	Major depressive disorder	6A70.3	Investigative	[16]
Piv-RYYRIK-NH2	DMVYNTB	Discovery agent	N.A.	Investigative	[12]
Pr-RYYRIK-NH2	DMKRMSP	Discovery agent	N.A.	Investigative	[12]
SB-612111	DM2SZ3F	Inflammation	1A00-CA43.1	Investigative	[16]
SCH-221510	DMHOUSR	Anxiety disorder	6B00-6B0Z	Investigative	[16]
SR-14136	DMPN3Q0	Pain	MG30-MG3Z	Investigative	[16]
Syn-1020	DMYTEXB	Pain	MG30-MG3Z	Investigative	[16]
T-BuAc-RYYRIK-NH2	DMKAX76	Discovery agent	N.A.	Investigative	[12]
UFP-101	DMKZF01	Discovery agent	N.A.	Investigative	[26]
UFP-112	DMENTMP	Discovery agent	N.A.	Investigative	[27]
Va-RYYRIK-NH2	DM3K8PT	Discovery agent	N.A.	Investigative	[12]
[Asp6,Lys10]N/OFQ(1-13)NH2	DMHJEQL	Discovery agent	N.A.	Investigative	[18]
[D-Asp7,Lys10]N/OFQ(1-13)NH2	DMSGW51	Discovery agent	N.A.	Investigative	[18]
[Nphe(1)]-nociceptin (1-13)-NH(2)	DMTG17Q	Discovery agent	N.A.	Investigative	[28]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Major depressive disorder	6A20	Pre-frontal cortex	1.75E-01	0.05	0.25

References

• [1] Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs. Biochemical Pharmacology Volume 95, Issue 2, 15 May 2015, Pages 81-97.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] 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.
• [4] Clinical pipeline report, company report or official report of Serodus ASA.
• [5] 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.
• [6] Nociceptin receptor antagonist JTC-801 inhibits nitrous oxide-induced analgesia in mice. J Anesth. 2009;23(2):301-3.
• [7] The nociceptin receptor as a potential target in drug design. Drug News Perspect. 2001 Aug;14(6):335-45.
• [8] Nocistatin and nociceptin given centrally induce opioid-mediated gastric mucosal protection. Peptides. 2008 Dec;29(12):2257-65.
• [9] 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.
• [10] Bioorg 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.
• [11] The discovery of tropane derivatives as nociceptin receptor ligands for the management of cough and anxiety. Bioorg Med Chem Lett. 2009 May 1;19(9):2519-23.
• [12] Designed modification of partial agonist of ORL1 nociceptin receptor for conversion into highly potent antagonist. Bioorg Med Chem. 2008 Mar 1;16(5):2635-44.
• [13] 3-(4-Piperidinyl)indoles and 3-(4-piperidinyl)pyrrolo-[2,3-b]pyridines as ligands for the ORL-1 receptor. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3524-8.
• [14] Synthesis and receptor binding properties of chimeric peptides containing a mu-opioid receptor ligand and nociceptin/orphanin FQ receptor ligand Ac... Bioorg Med Chem Lett. 2006 Sep 15;16(18):4839-41.
• [15] Pharmacological characterization of the nociceptin/orphanin FQ receptor non peptide antagonist Compound 24. Eur J Pharmacol. 2009 Jul 1;614(1-3):50-7.
• [16] 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: 320).
• [17] Structure-activity studies on nociceptin analogues: ORL1 receptor binding and biological activity of cyclic disulfide-containing analogues of nocic... J Med Chem. 2001 Nov 8;44(23):4015-8.
• [18] High affinity conformationally constrained nociceptin/orphanin FQ(1-13) amide analogues. J Med Chem. 2008 Aug 14;51(15):4385-7.
• [19] Novel, potent ORL-1 receptor agonist peptides containing alpha-Helix-promoting conformational constraints. J Med Chem. 2002 Nov 21;45(24):5280-6.
• [20] Synergistic effect of basic residues at positions 14-15 of nociceptin on binding affinity and receptor activation. Bioorg Med Chem. 2008 Oct 15;16(20):9261-7.
• [21] Discriminatory synergistic effect of Trp-substitutions in superagonist [(Arg/Lys)(14), (Arg/Lys)(15)]nociceptin on ORL1 receptor binding and activa... Bioorg Med Chem. 2009 Aug 1;17(15):5683-7.
• [22] Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5275-9.
• [23] Address 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.
• [24] Therapeutic applications of aptamers. Expert Opin Investig Drugs. 2008 Jan;17(1):43-60.
• [25] Ligands for kappa-opioid and ORL1 receptors identified from a conformationally constrained peptide combinatorial library. J Biol Chem. 1999 Sep 24;274(39):27513-22.
• [26] Nphe1,Arg14,Lys15nociceptin-NH2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor. Br J Pharmacol. 2002 May;136(2):303-11.
• [27] Pharmacological 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.
• [28] Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test. Naunyn Schmiedebergs Arch Pharmacol. 2002 Feb;365(2):164-7.