Target Information

Target General Information

Target ID

T52921 (Former ID: TTDR01247)

Target 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

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Gene Name

OPRL1

Target Type

Clinical trial target

[1]

Disease

[+] 4 Target-related Diseases

Atopic eczema [ICD-11: EA80]

Depression [ICD-11: 6A70-6A7Z]

Heart failure [ICD-11: BD10-BD1Z]

Headache [ICD-11: 8A80-8A84]

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.

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BioChemical Class

GPCR rhodopsin

UniProt ID

OPRX_HUMAN

Sequence

MEPLFPAPFWEVIYGSHLQGNLSLLSPNHSLLPPHLLLNASHGAFLPLGLKVTIVGLYLA
VCVGGLLGNCLVMYVILRHTKMKTATNIYIFNLALADTLVLLTLPFQGTDILLGFWPFGN
ALCKTVIAIDYYNMFTSTFTLTAMSVDRYVAICHPIRALDVRTSSKAQAVNVAIWALASV
VGVPVAIMGSAQVEDEEIECLVEIPTPQDYWGPVFAICIFLFSFIVPVLVISVCYSLMIR
RLRGVRLLSGSREKDRNLRRITRLVLVVVAVFVGCWTPVQVFVLAQGLGVQPSSETAVAI
LRFCTALGYVNSCLNPILYAFLDENFKACFRKFCCASALRRDVQVSDRVRSIAKDVALAC
KTSETVPRPA

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3D Structure

Click to Show 3D Structure of This Target

PDB

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

BTRX-246040

Drug Info

Phase 2

Major depressive disorder

[2]

LY-2940094

Drug Info

Phase 2

Major depressive disorder

[3]

PMX-53

Drug Info

Phase 2

Atopic dermatitis

[4], [5]

SER-100

Drug Info

Phase 2

Heart failure

[6]

NOCICEPTIN

Drug Info

Phase 1

Headache

[7]

Discontinued Drug(s)

[+] 2 Discontinued Drugs

JTC-801

Drug Info

Discontinued in Phase 2

Pain

[8], [9]

ND1251

Drug Info

Discontinued in Phase 1

Depression

[10]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

ATI-17000

Drug Info

Preclinical

Irritable bowel syndrome

[11]

Mode of Action

[+] 5 Modes of Action

Antagonist

[+] 10 Antagonist drugs

BTRX-246040

Drug Info

[2]

JTC-801

Drug Info

[17]

ATI-17000

Drug Info

[18], [19], [20]

Banyu Compound-24

Drug Info

[27]

BND-001

Drug Info

[28]

peptide III-BTD

Drug Info

[36]

PF-454583

Drug Info

[28]

SB-612111

Drug Info

[28]

UFP-101

Drug Info

[37]

[Nphe(1)]-nociceptin (1-13)-NH(2)

Drug Info

[20]

Modulator

[+] 1 Modulator drugs

LY-2940094

Drug Info

[1], [12]

Inhibitor

[+] 125 Inhibitor drugs

PMX-53

Drug Info

[13]

NOCICEPTIN

Drug Info

[15], [16]

1-(1,2-diphenylethyl)-4-phenylpiperidin-4-ol

Drug Info

[21]

1-(2-ethoxy-1-phenylethyl)-4-phenylpiperidin-4-ol

Drug Info

[21]

1-(3,3-diphenylpropyl)-4-phenylpiperidin-4-ol

Drug Info

[21]

1-(dio-tolylmethyl)-4-phenylpiperidin-4-ol

Drug Info

[21]

1-benzhydryl-4-(2-fluorophenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(2-methoxyphenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(3-fluorophenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(3-methoxyphenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(3-phenylpropyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(4-bromophenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(4-butylphenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(4-chlorophenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(4-ethylphenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(4-fluorophenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(4-methoxyphenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(4-propylphenyl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(benzyloxy)-4-phenylpiperidine

Drug Info

[21]

1-benzhydryl-4-(furan-2-yl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(pyridin-2-yl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-(thiophen-2-yl)piperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-benzylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-butylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-cyclohexylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-cyclopropylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-ethoxy-4-phenylpiperidine

Drug Info

[21]

1-benzhydryl-4-hexylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-isopropylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-m-tolylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-methoxy-4-phenylpiperidine

Drug Info

[21]

1-benzhydryl-4-o-tolylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-p-tolylpiperidin-4-ol

Drug Info

[22]

1-benzhydryl-4-phenyl-4-propoxypiperidine

Drug Info

[21]

1-benzhydryl-4-phenylpiperidin-4-ol

Drug Info

[23]

1-benzhydryl-4-tert-butylpiperidin-4-ol

Drug Info

[22]

1-benzyl-4-phenylpiperidin-4-ol

Drug Info

[21]

2,2-diMeBut-RYYRIK-NH2

Drug Info

[24]

2-MePen-RYYRIK-NH2

Drug Info

[24]

3-(1-benzylpiperidin-4-yl)-5-chloro-1H-indole

Drug Info

[25]

4-(2-(aminomethyl)phenyl)-1-benzylpiperidin-4-ol

Drug Info

[22]

4-phenyl-1-(1-phenylbutyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(1-phenylethyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(1-phenylheptyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(1-phenylhexyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(1-phenylpentyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(1-phenylpropan-2-yl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(1-phenylpropyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(3-phenylpropyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(phenyl(m-tolyl)methyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(phenyl(o-tolyl)methyl)piperidin-4-ol

Drug Info

[21]

4-phenyl-1-(phenyl(p-tolyl)methyl)piperidin-4-ol

Drug Info

[21]

Ac-RYYRIK-GGG-K-(NH2)-YAFGYPS-GG

Drug Info

[26]

Ac-RYYRIK-GGG-K-(NH2)-YRFB-GGGGG

Drug Info

[26]

Ac-RYYRIK-K-(NH2)-YAFGYPS

Drug Info

[26]

Ac-RYYRIK-K-(NH2)-YRFB

Drug Info

[26]

Ac-RYYRIK-NH2

Drug Info

[26]

Ada-RYYRIK-NH2

Drug Info

[24]

Bu-RYYRIK-NH2

Drug Info

[24]

Bz--RYYRIK-NH2

Drug Info

[24]

CFGGFTCARKSARK

Drug Info

[29]

CFGGFTGARKCARK

Drug Info

[29]

Cyclo-[Asp6,Lys10]N/OFQ(1-13)NH2

Drug Info

[30]

Cyclo[Cys6,Cys10]N/OFQ(1-13)NH2

Drug Info

[30]

Cyclo[Cys7,Cys10]N/OFQ(1-13)NH2

Drug Info

[30]

Cyclo[DAsp7,Lys10]N/OFQ(1-13)NH2

Drug Info

[30]

EtBut-RYYRIK-NH2

Drug Info

[24]

F-G-G-F-T-G-A-R-K-S-A-R-K-L-Aib-N-Q-CONH2

Drug Info

[31]

F-G-G-F-T-G-A-R-K-S-A-R-K-L-Aib-N-Q-COOH

Drug Info

[31]

F-G-G-F-T-G-A-R-K-S-A-R-K-L-MeA-N-Q-CONH2

Drug Info

[31]

F-G-G-F-T-G-A-R-K-S-A-R-K-L-MeA-N-Q-COOH

Drug Info

[31]

F-G-G-F-T-G-A-R-K-S-Aib-R-K-L-A-N-Q-CONH2

Drug Info

[31]

F-G-G-F-T-G-A-R-K-S-Aib-R-K-L-A-N-Q-COOH

Drug Info

[31]

F-G-G-F-T-G-A-R-K-S-MeA-R-K-L-A-N-Q-CONH2

Drug Info

[31]

F-G-G-F-T-G-A-R-K-S-MeA-R-K-L-A-N-Q-COOH

Drug Info

[31]

F-G-G-F-T-G-Aib-R-K-S-A-R-K-L-A-N-Q-CONH2

Drug Info

[31]

F-G-G-F-T-G-Aib-R-K-S-A-R-K-L-A-N-Q-COOH

Drug Info

[31]

F-G-G-F-T-G-Aib-R-K-S-Aib-R-K-L-A-N-Q-CONH2

Drug Info

[31]

F-G-G-F-T-G-MeA-R-K-S-A-R-K-L-A-N-Q-CONH2

Drug Info

[31]

F-G-G-F-T-G-MeA-R-K-S-A-R-K-L-A-N-Q-COOH

Drug Info

[31]

FGGFTCARKCARK

Drug Info

[29]

FGGFTGARKCARKC

Drug Info

[29]

FGGFTGARKRKRKLANQ

Drug Info

[16]

FGGFTGARKSARKAANQ

Drug Info

[16]

FGGFTGARKSARKFANQ

Drug Info

[16]

FGGFTGARKSARKKANQ

Drug Info

[16]

FGGFTGARKSARKKKNQ

Drug Info

[16]

FGGFTGARKSARKKRNQ

Drug Info

[16]

FGGFTGARKSARKKWNQ

Drug Info

[32]

FGGFTGARKSARKL

Drug Info

[29]

FGGFTGARKSARKLADE

Drug Info

[29]

FGGFTGARKSARKLARK

Drug Info

[16]

FGGFTGARKSARKLFNQ

Drug Info

[16]

FGGFTGARKSARKLKNQ

Drug Info

[16]

FGGFTGARKSARKLLNQ

Drug Info

[16]

FGGFTGARKSARKLRNQ

Drug Info

[16]

FGGFTGARKSARKLVNQ

Drug Info

[16]

FGGFTGARKSARKLWNQ

Drug Info

[32]

FGGFTGARKSARKLYNQ

Drug Info

[16]

100

FGGFTGARKSARKRANQ

Drug Info

[16]

101

FGGFTGARKSARKRKNQ

Drug Info

[32]

102

FGGFTGARKSARKRKRK

Drug Info

[16]

103

FGGFTGARKSARKRRNQ

Drug Info

[16]

104

FGGFTGARKSARKRWNQ

Drug Info

[32]

105

FGGFTGARKSARKVANQ

Drug Info

[16]

106

FGGFTGARKSARKWANQ

Drug Info

[32]

107

FGGFTGARKSARKWKNQ

Drug Info

[32]

108

FGGFTGARKSARKWRNQ

Drug Info

[32]

109

FGGFTGARKSARKYANQ

Drug Info

[16]

110

FGGFTGCRKSARKC

Drug Info

[29]

111

FGGFTGCRKSCRK

Drug Info

[29]

112

FGGFTRKRKSARKLANQ

Drug Info

[16]

113

FLUPERAMIDE

Drug Info

[33]

114

For-RYYRIK-NH2

Drug Info

[24]

115

H-RYYRIK-NH2

Drug Info

[24]

116

Hex-RYYRIK-NH2

Drug Info

[24]

117

IsoBu-RYYRIK-NH2

Drug Info

[24]

118

IsoVa-RYYRIK-NH2

Drug Info

[24]

119

MeBut-RYYRIK-NH2

Drug Info

[24]

120

Piv-RYYRIK-NH2

Drug Info

[24]

121

Pr-RYYRIK-NH2

Drug Info

[24]

122

T-BuAc-RYYRIK-NH2

Drug Info

[24]

123

Va-RYYRIK-NH2

Drug Info

[24]

124

[Asp6,Lys10]N/OFQ(1-13)NH2

Drug Info

[30]

125

[D-Asp7,Lys10]N/OFQ(1-13)NH2

Drug Info

[30]

Agonist

[+] 6 Agonist drugs

SER-100

Drug Info

[14]

ND1251

Drug Info

[18]

N/OFQ-(1-13)-NH2

Drug Info

[34], [29]

SCH-221510

Drug Info

[28]

Syn-1020

Drug Info

[28]

UFP-112

Drug Info

[38]

Binder

[+] 1 Binder drugs

SR-14136

Drug Info

[28]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

Top

Ligand Name: Oleic acid

Ligand Info

Structure Description

The crystal structure of nociceptin/orphanin FQ peptide receptor (NOP) in complex with C-35 (PSI Community Target)

PDB:5DHG

Method

X-ray diffraction

Resolution

3.00 Å

Mutation

Yes

[39]

PDB Sequence

PLGLKVTIVG

⁵⁶

LYLAVCVGGL

⁶⁶

LGNCLVMYVI

⁷⁶

LRHTKMKTAT

⁸⁶

NIYIFNLALA

⁹⁶

DTLVLLTLPF

¹⁰⁶

QGTDILLGFW

¹¹⁶

PFGNALCKTV

¹²⁶

IAIDYYNMFT

¹³⁶

STFTLTAMSV

¹⁴⁶

DRYVAICHPI

¹⁵⁶

VRTSSKAQAV

¹⁷⁰

NVAIWALASV

¹⁸⁰

VGVPVAIMGS

¹⁹⁰

AQVEDEEIEC

²⁰⁰

LVEIPTPQDY

²¹⁰

WGPVFAICIF

²²⁰

LFSFIVPVLV

²³⁰

ISVCYSLMIR

²⁴⁰

RLRGVRLLSG

²⁵⁰

SREKDRNLRR

²⁶⁰

ITRLVLVVVA

²⁷⁰

VFVGCWTPVQ

²⁸⁰

VFVLAQGLGV

²⁹⁰

QPSSETAVAI

³⁰⁰

LRFCTALGYV

³¹⁰

NSCLNPILYA

³²⁰

FLDENFKACF

³³⁰

Residue

Distance (Å)

TYR89

3.453

ASN120

4.859

ALA121

3.676

LYS124

2.978

THR125

4.128

PHE139

4.257

ALA143

3.557

Residue

Distance (Å)

VAL146

3.751

ASP147

2.606

ARG162

4.470

VAL170

3.788

ILE174

4.456

ALA186

3.732

ILE187

3.902

Click to View More Binding Site Information of This Target and Ligand Pair

Ligand Name: SB-612111

Ligand Info

Structure Description

The crystal structure of nociceptin/orphanin FQ peptide receptor (NOP) in complex with SB-612111 (PSI Community Target)

PDB:5DHH

Method

X-ray diffraction

Resolution

3.00 Å

Mutation

Yes

[39]

PDB Sequence

FLPLGLKVTI

⁵⁴

VGLYLAVCVG

⁶⁴

GLLGNCLVMY

⁷⁴

VILRHTKMKT

⁸⁴

ATNIYIFNLA

⁹⁴

LADTLVLLTL

¹⁰⁴

PFQGTDILLG

¹¹⁴

FWPFGNALCK

¹²⁴

TVIAIDYYNM

¹³⁴

FTSTFTLTAM

¹⁴⁴

SVDRYVAICH

¹⁵⁴

PRTSSKAQAV

¹⁷⁰

NVAIWALASV

¹⁸⁰

VGVPVAIMGS

¹⁹⁰

AQVEDEEIEC

²⁰⁰

LVEIPTPQDY

²¹⁰

WGPVFAICIF

²²⁰

LFSFIVPVLV

²³⁰

ISVCYSLMIR

²⁴⁰

RLRGVRLLSG

²⁵⁰

SREKDRNLRR

²⁶⁰

ITRLVLVVVA

²⁷⁰

VFVGCWTPVQ

²⁸⁰

VFVLAQGLGV

²⁹⁰

QPSSETAVAI

³⁰⁰

LRFCTALGYV

³¹⁰

NSCLNPILYA

³²⁰

FLDENFKACF

³³⁰

Residue

Distance (Å)

GLN107

3.334

ASP110

3.376

ILE111

3.999

TRP116

3.949

VAL126

4.527

ILE127

3.584

ASP130

2.777

TYR131

3.461

MET134

4.048

CYS200

3.738

Residue

Distance (Å)

ILE219

3.342

SER223

3.768

TRP276

4.377

VAL279

3.138

GLN280

3.286

VAL283

3.317

ARG302

3.902

THR305

3.895

TYR309

3.647

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Olfactory receptor 6C70 (OR6C70)	PF13853	21.386 (71/332)	2.88E-09
Olfactory receptor 2T11 (OR2T11)	PF13853	23.494 (78/332)	3.96E-08
Olfactory receptor 2A1/2A42 (OR2A1; OR2A42)	PF13853	23.051 (68/295)	4.58E-08
Olfactory receptor 1J1 (OR1J1)	PF13853	28.571 (44/154)	4.23E-07
Olfactory receptor 6V1 (OR6V1)	PF13853	25.874 (37/143)	4.43E-07
Olfactory receptor 2M3 (OR2M3)	PF13853	23.183 (67/289)	4.96E-07
Olfactory receptor 2M7 (OR2M7)	PF13853	23.759 (67/282)	6.80E-07
Olfactory receptor 2S2 (OR2S2)	PF13853	24.662 (73/296)	1.02E-06
Olfactory receptor 2T4 (OR2T4)	PF13853	21.726 (73/336)	1.22E-06
Olfactory receptor 10H2 (OR10H2)	PF13853	30.833 (37/120)	1.63E-06
Olfactory receptor 2A14 (OR2A14)	PF13853	23.077 (72/312)	1.69E-06
Olfactory receptor 1J2 (OR1J2)	PF13853	29.457 (38/129)	1.94E-06
Olfactory receptor 10H4 (OR10H4)	PF13853	31.405 (38/121)	2.12E-06
Olfactory receptor 10G9 (OR10G9)	PF13853	28.467 (39/137)	2.14E-06
Olfactory receptor 14I1 (OR14I1)	PF13853	31.008 (40/129)	2.20E-06
Olfactory receptor 10G4 (OR10G4)	PF13853	27.848 (44/158)	2.24E-06
Olfactory receptor 10J1 (OR10J1)	PF13853	27.273 (39/143)	2.27E-06
Olfactory receptor 2T8 (OR2T8)	PF13853	28.462 (37/130)	2.62E-06
Olfactory receptor 10H1 (OR10H1)	PF13853	32.609 (45/138)	2.67E-06
Olfactory receptor 2M2 (OR2M2)	PF13853	27.950 (45/161)	2.79E-06
Putative olfactory receptor 1F12P (OR1F12P)	PF13853	22.408 (67/299)	4.64E-06
Olfactory receptor 2T33 (OR2T33)	PF13853	21.528 (62/288)	5.32E-06
Olfactory receptor 8B12 (OR8B12)	PF13853	20.202 (60/297)	5.73E-06
Olfactory receptor 2M5 (OR2M5)	PF13853	22.837 (66/289)	5.87E-06
Olfactory receptor 10H5 (OR10H5)	PF13853	31.884 (44/138)	6.09E-06
Olfactory receptor 6S1 (OR6S1)	PF13853	30.409 (52/171)	8.76E-06
Putative olfactory receptor 10D4 (OR10D4P)	PF13853	25.000 (40/160)	8.98E-06
Olfactory receptor 2M4 (OR2M4)	PF13853	25.694 (74/288)	1.01E-05
Olfactory receptor 10G8 (OR10G8)	PF13853	27.545 (46/167)	1.35E-05
Olfactory receptor 10G7 (OR10G7)	PF13853	27.215 (43/158)	1.45E-05
Olfactory receptor 2B2 (OR2B2)	PF13853	21.457 (53/247)	2.36E-05
Olfactory receptor 2T10 (OR2T10)	PF13853	24.402 (51/209)	2.37E-05
Olfactory receptor 2D2 (OR2D2)	PF13853	23.263 (77/331)	2.96E-05
Olfactory receptor 7A10 (OR7A10)	PF13853	21.886 (65/297)	3.33E-05
Olfactory receptor 51V1 (OR51V1)	PF13853	29.464 (33/112)	3.88E-05
Olfactory receptor 10A7 (OR10A7)	PF13853	23.077 (39/169)	4.00E-05
Olfactory receptor 10Q1 (OR10Q1)	PF13853	21.352 (60/281)	4.33E-05
Olfactory receptor 2T12 (OR2T12)	PF13853	21.575 (63/292)	4.35E-05
Olfactory receptor 2A25 (OR2A25)	PF13853	28.926 (35/121)	4.49E-05
Olfactory receptor 7A5 (OR7A5)	PF13853	24.444 (33/135)	4.70E-05
Olfactory receptor 52B6 (OR52B6)	PF13853	32.039 (33/103)	4.95E-05
Olfactory receptor 6C76 (OR6C76)	PF13853	21.284 (63/296)	5.60E-05
Olfactory receptor 1I1 (OR1I1)	PF13853	28.846 (30/104)	7.38E-05
Olfactory receptor 4E1 (OR4E1)	PF13853	25.714 (36/140)	8.08E-05
Olfactory receptor 2T3 (OR2T3)	PF13853	23.415 (48/205)	8.22E-05
Olfactory receptor 7G2 (OR7G2)	PF13853	28.440 (31/109)	8.28E-05
Putative olfactory receptor 2B3 (OR2B3)	PF13853	22.257 (71/319)	8.40E-05
Olfactory receptor 6B1 (OR6B1)	PF13853	22.794 (31/136)	8.57E-05
Olfactory receptor 1E2 (OR1E2)	PF13853	28.244 (37/131)	9.61E-05
Olfactory receptor 4K2 (OR4K2)	PF13853	28.571 (44/154)	9.71E-05
Olfactory receptor 1E1 (OR1E1)	PF13853	26.144 (40/153)	1.06E-04
Olfactory receptor 2H2 (OR2H2)	PF13853	22.601 (73/323)	1.07E-04
Olfactory receptor 10J3 (OR10J3)	PF13853	25.581 (33/129)	1.11E-04
Olfactory receptor 7G1 (OR7G1)	PF13853	26.056 (37/142)	1.12E-04
Olfactory receptor 2AT4 (OR2AT4)	PF13853	25.547 (35/137)	1.17E-04
Olfactory receptor 5K2 (OR5K2)	PF13853	27.679 (31/112)	1.24E-04
Olfactory receptor 51M1 (OR51M1)	PF13853	22.115 (46/208)	1.57E-04
Olfactory receptor 5K1 (OR5K1)	PF13853	27.679 (31/112)	1.60E-04
Olfactory receptor 2T7 (OR2T7)	PF13853	25.342 (74/292)	1.62E-04
Olfactory receptor 2A5 (OR2A5)	PF13853	20.656 (63/305)	1.69E-04
Olfactory receptor 52Z1P (OR52Z1P)	PF13853	28.947 (33/114)	1.70E-04
Olfactory receptor 2T34 (OR2T34)	PF13853	23.415 (48/205)	1.74E-04
Olfactory receptor 1G1 (OR1G1)	PF13853	28.972 (31/107)	2.30E-04
Olfactory receptor 6C68 (OR6C68)	PF13853	20.642 (45/218)	2.42E-04
Olfactory receptor 6C65 (OR6C65)	PF13853	20.476 (43/210)	2.51E-04
Olfactory receptor 2T29 (OR2T29)	PF13853	21.993 (64/291)	3.19E-04
Olfactory receptor 2T5 (OR2T5)	PF13853	21.993 (64/291)	3.19E-04
Olfactory receptor 51G2 (OR51G2)	PF13853	27.273 (27/99)	3.24E-04
Olfactory receptor 2T2 (OR2T2)	PF13853	22.699 (74/326)	3.47E-04
Olfactory receptor 4K15 (OR4K15)	PF13853	29.927 (41/137)	3.66E-04
Olfactory receptor 52H1 (OR52H1)	PF13853	29.703 (30/101)	3.75E-04
Olfactory receptor 1C1 (OR1C1)	PF13853	29.808 (31/104)	4.04E-04
Olfactory receptor 11G2 (OR11G2)	PF13853	24.762 (52/210)	4.30E-04
Olfactory receptor 10A2 (OR10A2)	PF13853	28.758 (44/153)	5.46E-04
Olfactory receptor 13A1 (OR13A1)	PF13853	20.930 (63/301)	5.61E-04
Olfactory receptor 2T35 (OR2T35)	PF13853	21.683 (67/309)	5.79E-04
Olfactory receptor 10G3 (OR10G3)	PF13853	26.531 (39/147)	6.40E-04
Olfactory receptor 4D9 (OR4D9)	PF13853	21.725 (68/313)	6.42E-04
Putative olfactory receptor 10D3 (OR10D3)	PF13853	23.571 (33/140)	6.98E-04
Olfactory receptor 7A17 (OR7A17)	PF13853	23.944 (34/142)	7.18E-04
Olfactory receptor 51E1 (OR51E1)	PF13853	31.304 (36/115)	8.15E-04
Olfactory receptor 7E24 (OR7E24)	PF13853	27.027 (30/111)	8.33E-04
Olfactory receptor 4C16 (OR4C16)	PF13853	26.718 (35/131)	8.45E-04
Olfactory receptor 51E2 (OR51E2)	PF13853	25.185 (34/135)	8.50E-04
Olfactory receptor 5AC1 (OR5AC1)	PF13853	28.571 (32/112)	1.00E-03
Olfactory receptor 7D2 (OR7D2)	PF13853	21.782 (66/303)	1.00E-03
Olfactory receptor 1M1 (OR1M1)	PF13853	20.513 (64/312)	1.00E-03
Olfactory receptor 7D4 (OR7D4)	PF13853	25.000 (29/116)	1.00E-03
Olfactory receptor 4S1 (OR4S1)	PF13853	28.829 (32/111)	1.00E-03
Putative olfactory receptor 52L2 (OR52L2P)	PF13853	29.839 (37/124)	1.00E-03
Olfactory receptor 7C1 (OR7C1)	PF13853	28.244 (37/131)	1.00E-03
Olfactory receptor 6C2 (OR6C2)	PF13853	21.845 (45/206)	1.00E-03
Olfactory receptor 1J4 (OR1J4)	PF13853	28.346 (36/127)	1.00E-03
Olfactory receptor 4D10 (OR4D10)	PF13853	25.688 (28/109)	1.00E-03
Olfactory receptor 11H7 (OR11H7)	PF13853	21.338 (67/314)	1.00E-03
Olfactory receptor 51B5 (OR51B5)	PF13853	19.905 (42/211)	2.00E-03
Olfactory receptor 5M10 (OR5M10)	PF13853	25.926 (35/135)	2.00E-03
Olfactory receptor 51F1 (OR51F1)	PF13853	26.797 (41/153)	2.00E-03
Olfactory receptor 4Q3 (OR4Q3)	PF13853	28.829 (32/111)	2.00E-03
Olfactory receptor 52B4 (OR52B4)	PF13853	26.667 (32/120)	2.00E-03
Olfactory receptor 2K2 (OR2K2)	PF13853	27.966 (33/118)	2.00E-03
Olfactory receptor 9Q1 (OR9Q1)	PF13853	24.211 (69/285)	2.00E-03
Olfactory receptor 2AJ1 (OR2AJ1)	PF13853	22.414 (65/290)	2.00E-03
Olfactory receptor 51D1 (OR51D1)	PF13853	24.074 (26/108)	3.00E-03
Olfactory receptor 13C8 (OR13C8)	PF13853	21.895 (67/306)	3.00E-03
Olfactory receptor 10AC1 (OR10AC1)	PF13853	47.059 (24/51)	3.00E-03
Olfactory receptor 10H3 (OR10H3)	PF13853	29.032 (27/93)	3.00E-03
Olfactory receptor 2C3 (OR2C3)	PF13853	23.684 (72/304)	3.00E-03
Olfactory receptor 14A2 (OR14A2)	PF13853	23.485 (31/132)	3.00E-03
Olfactory receptor 2T27 (OR2T27)	PF13853	24.878 (51/205)	3.00E-03
Olfactory receptor 2V2 (OR2V2)	PF13853	22.028 (63/286)	3.00E-03
Olfactory receptor 2V1 (OR2V1)	PF13853	21.352 (60/281)	4.00E-03
Olfactory receptor 11H4 (OR11H4)	PF13853	24.161 (36/149)	4.00E-03
Olfactory receptor 52P1 (OR52P1)	PF13853	39.286 (22/56)	4.00E-03
Olfactory receptor 8B8 (OR8B8)	PF13853	19.048 (56/294)	4.00E-03
Click to Show/Hide the Information of Human Similarity Proteins

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Neuroactive ligand-receptor interaction	hsa04080	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy

Degree	1	Degree centrality	1.07E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.07E-04	Radiality	3.98E-03	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.00E+00	Topological coefficient	.	Eccentricity	1
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Neuroactive ligand-receptor interaction

Panther Pathway

[+] 2 Panther Pathways

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

[+] 2 Reactome Pathways

Peptide ligand-binding receptors

G alpha (i) signalling events

WikiPathways

[+] 4 WikiPathways

GPCRs, Class A Rhodopsin-like

Peptide GPCRs

GPCR ligand binding

GPCR downstream signaling

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs. Biochemical Pharmacology Volume 95, Issue 2, 15 May 2015, Pages 81-97.

REF 2

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 3

ClinicalTrials.gov (NCT01724112) Study of the Efficacy and Safety of LY2940094 in Participants With Major Depressive Disorder (MDD). U.S. National Institutes of Health.

REF 4

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. (Ligand id: 579).

REF 5

PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2 (MrgX2) in human mast cells. Mol Pharmacol. 2011 Jun;79(6):1005-13.

REF 6

ClinicalTrials.gov (NCT00283361) ZP120 Add-on to Furosemide in Treatment of Acute or Sub-Acute Decompensated Heart Failure. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT01404091) A Study of Nociceptin/Orphanin FQ Peptide Receptor Occupancy in Healthy Subjects. U.S. National Institutes of Health.

REF 8

REF 9

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016171)

REF 10

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020720)

REF 11

Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.

REF 12

UK Journal of Pharmaceutical and Biosciences Vol. 3(1), 12-17, 2015.

REF 13

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.

REF 14

Clinical pipeline report, company report or official report of Serodus ASA.

REF 15

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.

REF 16

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.

REF 17

Nociceptin receptor antagonist JTC-801 inhibits nitrous oxide-induced analgesia in mice. J Anesth. 2009;23(2):301-3.

REF 18

The nociceptin receptor as a potential target in drug design. Drug News Perspect. 2001 Aug;14(6):335-45.

REF 19

Nocistatin and nociceptin given centrally induce opioid-mediated gastric mucosal protection. Peptides. 2008 Dec;29(12):2257-65.

REF 20

Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test. Naunyn Schmiedebergs Arch Pharmacol. 2002 Feb;365(2):164-7.

REF 21

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.

REF 22

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.

REF 23

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.

REF 24

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.

REF 25

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.

REF 26

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.

REF 27

Pharmacological characterization of the nociceptin/orphanin FQ receptor non peptide antagonist Compound 24. Eur J Pharmacol. 2009 Jul 1;614(1-3):50-7.

REF 28

REF 29

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.

REF 30

High affinity conformationally constrained nociceptin/orphanin FQ(1-13) amide analogues. J Med Chem. 2008 Aug 14;51(15):4385-7.

REF 31

Novel, potent ORL-1 receptor agonist peptides containing alpha-Helix-promoting conformational constraints. J Med Chem. 2002 Nov 21;45(24):5280-6.

REF 32

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.

REF 33

Design and synthesis of 4-phenyl piperidine compounds targeting the mu receptor. Bioorg Med Chem Lett. 2004 Nov 1;14(21):5275-9.

REF 34

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.

REF 35

Therapeutic applications of aptamers. Expert Opin Investig Drugs. 2008 Jan;17(1):43-60.

REF 36

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.

REF 37

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.

REF 38

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.

REF 39

The Importance of Ligand-Receptor Conformational Pairs in Stabilization: Spotlight on the N/OFQ G Protein-Coupled Receptor. Structure. 2015 Dec 1;23(12):2291-2299.

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