Target Information

Target General Information

Target ID

T66665

Target Name

Prostaglandin G/H synthase 2 (COX-2)

Synonyms

Prostaglandin-endoperoxide synthase 2; Prostaglandin H2 synthase 2; PHS II; PGHS-2; PGH synthase 2; Cyclooxygenase-2; COX2; COX-2

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Gene Name

PTGS2

Target Type

Successful target

[1]

Disease

[+] 9 Target-related Diseases

Chronic pain [ICD-11: MG30]

Female pelvic pain [ICD-11: GA34]

Hyper-lipoproteinaemia [ICD-11: 5C80]

Indeterminate colitis [ICD-11: DD72]

Knee osteoarthritis [ICD-11: FA01]

Osteoarthritis [ICD-11: FA00-FA05]

Pain [ICD-11: MG30-MG3Z]

Rheumatoid arthritis [ICD-11: FA20]

Tuberculosis [ICD-11: 1B10-1B12]

Function

Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis. During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, that regulates phagocytic microglia (By similarity).

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BioChemical Class

Paired donor oxygen oxidoreductase

UniProt ID

PGH2_HUMAN

EC Number

EC 1.14.99.1

Sequence

MLARALLLCAVLALSHTANPCCSHPCQNRGVCMSVGFDQYKCDCTRTGFYGENCSTPEFL
TRIKLFLKPTPNTVHYILTHFKGFWNVVNNIPFLRNAIMSYVLTSRSHLIDSPPTYNADY
GYKSWEAFSNLSYYTRALPPVPDDCPTPLGVKGKKQLPDSNEIVEKLLLRRKFIPDPQGS
NMMFAFFAQHFTHQFFKTDHKRGPAFTNGLGHGVDLNHIYGETLARQRKLRLFKDGKMKY
QIIDGEMYPPTVKDTQAEMIYPPQVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCD
VLKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNKQFQYQ
NRIAAEFNTLYHWHPLLPDTFQIHDQKYNYQQFIYNNSILLEHGITQFVESFTRQIAGRV
AGGRNVPPAVQKVSQASIDQSRQMKYQSFNEYRKRFMLKPYESFEELTGEKEMSAELEAL
YGDIDAVELYPALLVEKPRPDAIFGETMVEVGAPFSLKGLMGNVICSPAYWKPSTFGGEV
GFQIINTASIQSLICNNVKGCPFTSFSVPDPELIKTVTINASSSRSGLDDINPTVLLKER
STEL

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T08Q7W

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 25 Approved Drugs

Aminosalicylic Acid

Drug Info

Approved

Pulmonary and extrapulmonary tuberculosis

[4]

Carprofen

Drug Info

Approved

Pain

[5], [6]

Celecoxib

Drug Info

Approved

Rheumatoid arthritis

[7], [8]

Diflunisal

Drug Info

Approved

Pain

[9], [10]

Eicosapentaenoic acid/docosa-hexaenoic acid

Drug Info

Approved

Hypertriglyceridemia

[11]

Etodolac

Drug Info

Approved

Pain

[12], [13]

Etoricoxib

Drug Info

Approved

Rheumatoid arthritis

[14], [15]

FENBUFEN

Drug Info

Approved

Arthritis

[4]

Flufenamic Acid

Drug Info

Approved

Dysmenorrhea

[4], [16]

Flurbiprofen

Drug Info

Approved

Rheumatoid arthritis

[17], [18]

Ibuprofen

Drug Info

Approved

Pain

[8], [19]

Indomethacin

Drug Info

Approved

Rheumatoid arthritis

[4]

Lumiracoxib

Drug Info

Approved

Knee osteoarthritis

[15], [20]

Meclofenamate Sodium

Drug Info

Approved

Arthritis

[4]

Mefenamic acid

Drug Info

Approved

Dysmenorrhea

[4], [21], [22]

Meloxicam

Drug Info

Approved

Arthritis

[4], [23], [24]

Nabumetone

Drug Info

Approved

Pain

[25], [26]

Naproxen

Drug Info

Approved

Osteoarthritis

[4]

Niflumic Acid

Drug Info

Approved

Rheumatoid arthritis

[4], [27], [28]

Phenylbutazone

Drug Info

Approved

Chronic pain

[4], [29], [30]

Rofecoxib

Drug Info

Approved

Osteoarthritis

[31], [8]

Tenoxicam

Drug Info

Approved

Rheumatoid arthritis

[32], [33], [34]

Tiaprofenic acid

Drug Info

Approved

Pain

[35], [4]

Tolmetin

Drug Info

Approved

Rheumatoid arthritis

[4], [36], [37]

Valdecoxib

Drug Info

Approved

Osteoarthritis

[38], [39]

Clinical Trial Drug(s)

[+] 6 Clinical Trial Drugs

(S)-FLURBIPROFEN

Drug Info

Preregistration

Myalgia

[40]

Curcumin

Drug Info

Phase 3

Solid tumour/cancer

[43], [44]

ThermoProfen

Drug Info

Phase 3

Pain

[45]

Darbufelone

Drug Info

Phase 2/3

Asthma

[46]

SC-75416

Drug Info

Phase 2

Pain

[49]

RWJ-67657

Drug Info

Phase 1

Arthritis

[51]

Discontinued Drug(s)

[+] 25 Discontinued Drugs

INDOPROFEN

Drug Info

Withdrawn from market

Gout

[4]

GW-406381

Drug Info

Discontinued in Phase 3

Neuropathic pain

[53]

PMI-001

Drug Info

Discontinued in Phase 3

Lupus

[54]

Apricoxib

Drug Info

Discontinued in Phase 2

Rheumatoid arthritis

[56]

CRx-401

Drug Info

Discontinued in Phase 2

Type-2 diabetes

[57]

GSK-644784

Drug Info

Discontinued in Phase 2

Neuropathic pain

[53]

RQ-00317076

Drug Info

Discontinued in Phase 2

Pain

[58]

S-2474

Drug Info

Discontinued in Phase 2

Rheumatoid arthritis

[59]

TEBUFELONE

Drug Info

Discontinued in Phase 2

Pain

[60]

DUP 697

Drug Info

Discontinued in Phase 1

Pain

[61]

E-6087

Drug Info

Discontinued in Phase 1

Pain

[62]

GR-253035

Drug Info

Discontinued in Phase 1

Alzheimer disease

[63]

SC-57666

Drug Info

Discontinued in Phase 1

Rheumatoid arthritis

[64]

ATLIPROFEN METHYL ESTER

Drug Info

Terminated

Inflammation

[66]

Flosulide

Drug Info

Terminated

Pain

[67]

FR-123826

Drug Info

Terminated

Rheumatoid arthritis

[68]

L-745337

Drug Info

Terminated

Asthma

[69]

L-768277

Drug Info

Terminated

Hyperthermia

[70]

Nimesulide

Drug Info

Terminated

Metastatic colorectal cancer

[71]

NS398

Drug Info

Terminated

Endometriosis

[72]

ON-09300

Drug Info

Terminated

Solid tumour/cancer

[73]

RPR 200765A

Drug Info

Terminated

Rheumatoid arthritis

[74]

RWJ-63556

Drug Info

Terminated

Arthritis

[75]

S-33516

Drug Info

Terminated

Arthritis

[76]

SC-236

Drug Info

Terminated

Solid tumour/cancer

[77]

Mode of Action

[+] 3 Modes of Action

Modulator

[+] 13 Modulator drugs

Aminosalicylic Acid

Drug Info

[78]

Flurbiprofen

Drug Info

[90]

Indomethacin

Drug Info

[78]

Meclofenamate Sodium

Drug Info

[95]

Darbufelone

Drug Info

[46]

GR-253035

Drug Info

[125]

ATLIPROFEN METHYL ESTER

Drug Info

[78]

Flosulide

Drug Info

[126]

L-745337

Drug Info

[128]

L-768277

Drug Info

[129]

ON-09300

Drug Info

[78]

RWJ-63556

Drug Info

[75]

Nitroflurbiprofen

Drug Info

[174], [90], [175]

Inhibitor

[+] 153 Inhibitor drugs

Carprofen

Drug Info

[79]

Celecoxib

Drug Info

[80], [81], [82]

Diflunisal

Drug Info

[1]

Eicosapentaenoic acid/docosa-hexaenoic acid

Drug Info

[83]

Etodolac

Drug Info

[84], [85]

Etoricoxib

Drug Info

[86], [87]

FENBUFEN

Drug Info

[88]

Flufenamic Acid

Drug Info

[89]

Ibuprofen

Drug Info

[91], [92], [93]

Lumiracoxib

Drug Info

[94]

Mefenamic acid

Drug Info

[96]

Meloxicam

Drug Info

[97]

Nabumetone

Drug Info

[98]

Naproxen

Drug Info

[99], [8]

Niflumic Acid

Drug Info

[100]

Phenylbutazone

Drug Info

[101]

Rofecoxib

Drug Info

[82], [102], [103], [104], [105]

Tenoxicam

Drug Info

[106], [107]

Tiaprofenic acid

Drug Info

[108]

Tolmetin

Drug Info

[91]

Valdecoxib

Drug Info

[39]

IMRECOXIB

Drug Info

[109]

(S)-FLURBIPROFEN

Drug Info

[110]

Curcumin

Drug Info

[111]

ThermoProfen

Drug Info

[112]

SC-75416

Drug Info

[113]

RWJ-67657

Drug Info

[114]

Carbamate derivative 2

Drug Info

[115]

PMID29130358-Compound-LonimacranthoideVI

Drug Info

[116]

INDOPROFEN

Drug Info

[110]

GW-406381

Drug Info

[53]

PMI-001

Drug Info

[117]

Apricoxib

Drug Info

[118]

CRx-401

Drug Info

[119]

GSK-644784

Drug Info

[53]

RQ-00317076

Drug Info

[120]

S-2474

Drug Info

[121]

TEBUFELONE

Drug Info

[122]

DUP 697

Drug Info

[123]

E-6087

Drug Info

[124], [4]

SC-57666

Drug Info

[122]

FR-123826

Drug Info

[127]

Nimesulide

Drug Info

[130]

NS398

Drug Info

[8]

RPR 200765A

Drug Info

[131]

S-33516

Drug Info

[132]

SB 203580

Drug Info

[133]

SC-236

Drug Info

[134]

SC-58125

Drug Info

[135]

SC-58451

Drug Info

[136]

(11H-Dibenzo[b,e][1,4]dioxepin-2-yl)-acetic acid

Drug Info

[137]

(11H-Dibenzo[b,e][1,4]dioxepin-8-yl)-acetic acid

Drug Info

[137]

(E)-2-(4-(methylsulfonyl)styryl)thiophene

Drug Info

[138]

(E)-3-(4-(methylsulfonyl)styryl)thiophene

Drug Info

[138]

(E)-4-(2-(furan-2-yl)vinyl)benzenesulfonamide

Drug Info

[138]

(E)-4-(2-(thiophen-2-yl)vinyl)benzenesulfonamide

Drug Info

[138]

(E)-4-(2-(thiophen-3-yl)vinyl)benzenesulfonamide

Drug Info

[138]

(R)-2-(4-Isobutyl-phenyl)-N-phenyl-propionamide

Drug Info

[110]

(Z)-2'-des-methyl sulindac sulfide

Drug Info

[139]

1,2-dihydro-3-(2,3,4-trimethoxyphenyl)naphthalene

Drug Info

[140]

1,3-bis(nitrooxy)propan-2-yl 2-acetoxybenzoate

Drug Info

[141]

1-(2-hydroxyphenyl)-3-p-tolylprop-2-en-1-one

Drug Info

[142]

1-(4-(methylsulfonyl)phenyl)-1H-indole

Drug Info

[143]

1-(4-(methylsulfonyl)phenyl)-1H-pyrrole

Drug Info

[143]

1-(4-(methylsulfonyl)phenyl)-3-p-tolylurea

Drug Info

[144]

1-(4-(methylsulfonyl)phenyl)-3-phenylurea

Drug Info

[144]

2'-hydroxy-3,4,5-trimethoxychalcone

Drug Info

[142]

2'-Hydroxychalcone

Drug Info

[142]

2,3-dimethoxy-2'-hydroxychalcone

Drug Info

[142]

2,4'-Dimethoxy-5,3'-di-(2-propenyl)-biphenyl

Drug Info

[145]

2,4'-Dimethoxy-5,3'-dipropyl-biphenyl

Drug Info

[145]

2,4-dimethoxy-2'-hydroxychalcone

Drug Info

[142]

2,6-dihydroxy-1,7-dimethoxyxanthone

Drug Info

[146]

2-(2,3,4-trimethoxyphenyl)-1H-indene

Drug Info

[140]

2-(2-(2,6-dimethylphenylamino)phenyl)acetic acid

Drug Info

[147]

2-(3-Phenyl-propyl)-1,2-dihydro-indazol-3-one

Drug Info

[148]

2-(4-(methylsulfonyl)phenyl)pyridine

Drug Info

[143]

2-(N-(2-Ffuorophenyl)pyrrol-3-yl) acetic acid

Drug Info

[149]

2-(N-(2-fluorophenyl)pyrrol-2-yl) acetic acid

Drug Info

[149]

2-(p-Methylsulfonylbenzoyl)furan

Drug Info

[143]

2-Benzyl-1,2-dihydro-indazol-3-one

Drug Info

[148]

2-Furan-2-ylmethyl-1,2-dihydro-indazol-3-one

Drug Info

[148]

2-Phenethyl-1,2-dihydro-indazol-3-one

Drug Info

[148]

2-Phenyl-1,2-dihydro-indazol-3-one

Drug Info

[148]

3,4-dibenzyloxy-2'-hydroxychalcone

Drug Info

[142]

3,4-dihydroxyxanthone

Drug Info

[146]

3-(4-Methanesulfonyl-phenyl)-1-phenyl-propynone

Drug Info

[150]

3-benzyloxy-4-methoxy-2'-hydroxychalcone

Drug Info

[142]

3-Bromo-2'-hydroxy-4-methoxychalcone

Drug Info

[142]

4,5-Bis(4-chlorophenyl)-1,2-selenazole

Drug Info

[151]

4,5-Bis(4-chlorophenyl)isothiazole

Drug Info

[152]

4,5-Bis(4-methoxyphenyl)-1,2-selenazole

Drug Info

[151]

4,5-Bis(4-methoxyphenyl)isothiazole

Drug Info

[152]

4-(3-hydroxy-benzylideneamino)-benzenesulfonamide

Drug Info

[153]

4-(3-methoxy-benzylideneamino)-benzenesulfonamide

Drug Info

[153]

4-(3-nitro-benzylideneamino)-benzenesulfonamide

Drug Info

[153]

4-(4-Chlorophenyl)-5-p-tolyl-1,2-selenazole

Drug Info

[151]

4-(4-hydroxy-benzylideneamino)-benzenesulfonamide

Drug Info

[153]

4-(4-methoxy-benzylideneamino)-benzenesulfonamide

Drug Info

[153]

100

4-(4-methyl-benzylideneamino)-benzenesulfonamide

Drug Info

[153]

101

4-(4-methyl-phenyliminomethyl)-benzenesulfonamide

Drug Info

[153]

102

4-(4-nitro-benzylideneamino)-benzenesulfonamide

Drug Info

[153]

103

4-(benzylideneamino)benzenesulfonamide

Drug Info

[153]

104

4-amino-N-(4-chlorophenyl)benzenesulfonamide

Drug Info

[154]

105

4-amino-N-(4-iodophenyl)benzenesulfonamide

Drug Info

[154]

106

4-benzyloxy-2'-hydroxychalcone

Drug Info

[142]

107

4-fluoro-N-(4-(methylsulfonyl)phenyl)aniline

Drug Info

[143]

108

4-phenyliminomethyl-benzenesulfonamide

Drug Info

[153]

109

5,3'-Dipropyl-biphenyl-2,4'-diol

Drug Info

[145]

110

5-(2-Imidazol-1-yl-ethyl)-7,8-dihydro-quinoline

Drug Info

[155]

111

5-(4-Chlorophenyl)-4-p-tolyl-1,2-selenazole

Drug Info

[151]

112

5-(4-Methoxyphenyl)-4-p-tolyl-1,2-selenazole

Drug Info

[151]

113

5-Ethyl-3,4-diphenyl-isoxazole

Drug Info

[156]

114

5-methoxy-2-(4-(methylsulfonyl)phenyl)-1H-indole

Drug Info

[157]

115

5-Methyl-3,4-diphenyl-isoxazole

Drug Info

[156]

116

5-Phenyl-pentanoic acid benzyl-hydroxy-amide

Drug Info

[158]

117

5-thia-8,11,14,17-eicosatetraenoic acid

Drug Info

[83]

118

6,7'-oxybis(2-phenyl-4H-chromen-4-one)

Drug Info

[159]

119

alpha-linolenic acid

Drug Info

[83]

120

B-Octylglucoside

Drug Info

[160]

121

Bimetopyrole

Drug Info

[123]

122

CLEMATOMANDSHURICA SAPONIN A

Drug Info

[162]

123

CR-4174

Drug Info

[163]

124

DFU

Drug Info

[164]

125

Firocoxib

Drug Info

[165]

126

Furan-3-yl(4-(methylsulfonyl)phenyl)methanone

Drug Info

[143]

127

GW-637185X

Drug Info

[166]

128

HONOKIOL

Drug Info

[145]

129

L-748780

Drug Info

[167]

130

L-761000

Drug Info

[167]

131

LM-4108

Drug Info

[168]

132

METHYLHONOKIOL

Drug Info

[145]

133

Microxine

Drug Info

[169]

134

N-(1H-indazol-5-yl)acetamide

Drug Info

[170]

135

N-(3-(phenylthio)pyridin-4-yl)methanesulfonamide

Drug Info

[171]

136

N-(3-phenoxy-4-pyridinyl)ethanesulfonamide

Drug Info

[172]

137

N-(3-phenylamino-4-pyridinyl)methanesulfonamide

Drug Info

[171]

138

Nectamazin C

Drug Info

[173]

139

NEOLIGNAN 9-NOR-7,8-DEHYDRO-ISOLICARIN B

Drug Info

[173]

140

NSC-27236

Drug Info

[176]

141

Oxametacin

Drug Info

[177]

142

PHENIDONE

Drug Info

[148]

143

Prifelone

Drug Info

[178]

144

Primary alcohol metabolite of celecoxib

Drug Info

[179]

145

Prostaglandin G2

Drug Info

[180]

146

Resveratrol Potassium3-Sulfate

Drug Info

[181]

147

Resveratrol Potassium4,-Sulfate

Drug Info

[181]

148

SB 239063

Drug Info

[182]

149

SC-558

Drug Info

[183]

150

TENOSAL

Drug Info

[184], [4]

151

THIOCTIC ACID

Drug Info

[151]

152

Wogonin

Drug Info

[142]

153

XGP-110

Drug Info

[163]

Regulator (upregulator)

[+] 1 Regulator (upregulator) drugs

C-myb

Drug Info

[161]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

Top

Ligand Name: Salicyclic acid

Ligand Info

Structure Description

The Crystal Structure of Salicylate Bound to Human Cyclooxygenase-2

PDB:5F1A

Method

X-ray diffraction

Resolution

2.38 Å

Mutation

[185]

PDB Sequence

KNPCCSHPCQ

⁴²

NRGVCMSVGF

⁵²

DQYKCDCTRT

⁶²

GFYGENCSTP

⁷²

EFLTRIKLFL

⁸²

KPTPNTVHYI

⁹²

LTHFKGFWNV

¹⁰²

VNNIPFLRNA

¹¹¹

IMSYVLTSRS

¹²¹

HLIDSPPTYN

¹³¹

ADYGYKSWEA

¹⁴¹

FSNLSYYTRA

¹⁵¹

LPPVPDDCPT

¹⁶¹

PLGVKGKKQL

¹⁷¹

PDSNEIVEKL

¹⁸¹

LLRRKFIPDP

¹⁹¹

QGSNMMFAFF

²⁰¹

AQHFTHQFFK

²¹¹

TDHKRGPAFT

²²¹

NGLGHGVDLN

²³¹

HIYGETLARQ

²⁴¹

RKLRLFKDGK

²⁵¹

MKYQIIDGEM

²⁶¹

YPPTVKDTQA

²⁷¹

EMIYPPQVPE

²⁸¹

HLRFAVGQEV

²⁹¹

FGLVPGLMMY

³⁰¹

ATIWLREHNR

³¹¹

VCDVLKQEHP

³²¹

EWGDEQLFQT

³³¹

SRLILIGETI

³⁴¹

KIVIEDYVQH

³⁵¹

LSGYHFKLKF

³⁶¹

DPELLFNKQF

³⁷¹

QYQNRIAAEF

³⁸¹

NTLYHWHPLL

³⁹¹

PDTFQIHDQK

⁴⁰¹

YNYQQFIYNN

⁴¹¹

SILLEHGITQ

⁴²¹

FVESFTRQIA

⁴³¹

GRVAGGRNVP

⁴⁴¹

PAVQKVSQAS

⁴⁵¹

IDQSRQMKYQ

⁴⁶¹

SFNEYRKRFM

⁴⁷¹

LKPYESFEEL

⁴⁸¹

TGEKEMSAEL

⁴⁹¹

EALYGDIDAV

⁵⁰¹

ELYPALLVEK

⁵¹¹

PRPDAIFGET

⁵²¹

MVEVGAPFSL

⁵³¹

KGLMGNVICS

⁵⁴¹

PAYWKPSTFG

⁵⁵¹

GEVGFQIINT

⁵⁶¹

ASIQSLICNN

⁵⁷¹

VKGCPFTSFS

⁵⁸¹

VPD

Residue

Distance (Å)

TYR348

4.500

VAL349

3.605

LEU352

3.489

PHE381

4.347

LEU384

3.734

TYR385

3.213

TRP387

3.232

Residue

Distance (Å)

PHE518

4.563

MET522

3.341

VAL523

4.114

GLY526

3.590

ALA527

3.606

SER530

3.350

Ligand Name: Mefenamic acid

Ligand Info

Structure Description

The Structure of Mefenamic Acid Bound to Human Cyclooxygenase-2

PDB:5IKR

Method

X-ray diffraction

Resolution

2.34 Å

Mutation

[186]

PDB Sequence

NPCCSHPCQN

⁴³

RGVCMSVGFD

⁵³

QYKCDCTRTG

⁶³

FYGENCSTPE

⁷³

FLTRIKLFLK

⁸³

PTPNTVHYIL

⁹³

THFKGFWNVV

¹⁰³

NNIPFLRNAI

¹¹²

MSYVLTSRSH

¹²²

LIDSPPTYNA

¹³²

DYGYKSWEAF

¹⁴²

SNLSYYTRAL

¹⁵²

PPVPDDCPTP

¹⁶²

LGVKGKKQLP

¹⁷²

DSNEIVEKLL

¹⁸²

LRRKFIPDPQ

¹⁹²

GSNMMFAFFA

²⁰²

QHFTHQFFKT

²¹²

DHKRGPAFTN

²²²

GLGHGVDLNH

²³²

IYGETLARQR

²⁴²

KLRLFKDGKM

²⁵²

KYQIIDGEMY

²⁶²

PPTVKDTQAE

²⁷²

MIYPPQVPEH

²⁸²

LRFAVGQEVF

²⁹²

GLVPGLMMYA

³⁰²

TIWLREHNRV

³¹²

CDVLKQEHPE

³²²

WGDEQLFQTS

³³²

RLILIGETIK

³⁴²

IVIEDYVQHL

³⁵²

SGYHFKLKFD

³⁶²

PELLFNKQFQ

³⁷²

YQNRIAAEFN

³⁸²

TLYHWHPLLP

³⁹²

DTFQIHDQKY

⁴⁰²

NYQQFIYNNS

⁴¹²

ILLEHGITQF

⁴²²

VESFTRQIAG

⁴³²

RVAGGRNVPP

⁴⁴²

AVQKVSQASI

⁴⁵²

DQSRQMKYQS

⁴⁶²

FNEYRKRFML

⁴⁷²

KPYESFEELT

⁴⁸²

GEKEMSAELE

⁴⁹²

ALYGDIDAVE

⁵⁰²

LYPALLVEKP

⁵¹²

RPDAIFGETM

⁵²²

VEVGAPFSLK

⁵³²

GLMGNVICSP

⁵⁴²

AYWKPSTFGG

⁵⁵²

EVGFQIINTA

⁵⁶²

SIQSLICNNV

⁵⁷²

KGCPFTSFSV

⁵⁸²

Residue

Distance (Å)

MET113

4.859

VAL116

3.364

ARG120

3.090

PHE205

4.772

VAL344

4.809

TYR348

3.093

VAL349

1.966

LEU352

2.227

SER353

2.935

TYR355

2.457

LEU359

3.497

PHE381

3.369

Residue

Distance (Å)

LEU384

2.946

TYR385

2.030

TRP387

2.143

PHE518

4.692

MET522

2.446

VAL523

2.322

GLU524

4.894

GLY526

2.729

ALA527

2.506

SER530

1.987

LEU531

2.212

LEU534

4.618

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
Neurexin-2 (NRXN2)	PF02210	42.222 (19/45)	2.73E-04

KEGG Pathway	Pathway ID	Affiliated Target
Arachidonic acid metabolism	hsa00590	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
NF-kappa B signaling pathway	hsa04064	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
VEGF signaling pathway	hsa04370	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
C-type lectin receptor signaling pathway	hsa04625	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
IL-17 signaling pathway	hsa04657	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
TNF signaling pathway	hsa04668	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Retrograde endocannabinoid signaling	hsa04723	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Serotonergic synapse	hsa04726	Affiliated Target
Class: Organismal Systems => Nervous system	Pathway Hierarchy
Ovarian steroidogenesis	hsa04913	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Oxytocin signaling pathway	hsa04921	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Regulation of lipolysis in adipocytes	hsa04923	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	11	Degree centrality	1.18E-03	Betweenness centrality	1.72E-03
Closeness centrality	2.39E-01	Radiality	1.42E+01	Clustering coefficient	1.09E-01
Neighborhood connectivity	4.11E+01	Topological coefficient	1.03E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(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

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Affiliated Biological Pathways

Top

BioCyc

[+] 4 BioCyc Pathways

Aspirin-triggered lipoxin biosynthesis

Aspirin triggered resolvin D biosynthesis

C20 prostanoid biosynthesis

Aspirin triggered resolvin E biosynthesis

KEGG Pathway

[+] 15 KEGG Pathways

Arachidonic acid metabolism

Metabolic pathways

NF-kappa B signaling pathway

VEGF signaling pathway

TNF signaling pathway

Retrograde endocannabinoid signaling

Serotonergic synapse

Ovarian steroidogenesis

Oxytocin signaling pathway

Regulation of lipolysis in adipocytes

Leishmaniasis

Pathways in cancer

Chemical carcinogenesis

MicroRNAs in cancer

Small cell lung cancer

NetPath Pathway

[+] 5 NetPath Pathways

IL1 Signaling Pathway

TSH Signaling Pathway

IL4 Signaling Pathway

TGF_beta_Receptor Signaling Pathway

IL5 Signaling Pathway

Panther Pathway

[+] 4 Panther Pathways

Endothelin signaling pathway

Inflammation mediated by chemokine and cytokine signaling pathway

Toll receptor signaling pathway

CCKR signaling map ST

Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Arachidonic Acid Metabolism

PID Pathway

[+] 5 PID Pathways

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

S1P1 pathway

C-MYB transcription factor network

Signaling mediated by p38-alpha and p38-beta

Calcium signaling in the CD4+ TCR pathway

WikiPathways

[+] 8 WikiPathways

Prostaglandin Synthesis and Regulation

Arachidonic acid metabolism

Aryl Hydrocarbon Receptor

Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis

Spinal Cord Injury

Integrated Pancreatic Cancer Pathway

Eicosanoid Synthesis

Selenium Micronutrient Network

References

Top

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