Target Information

Target General Information

Target ID

T80975 (Former ID: TTDS00008)

Target Name

Vascular endothelial growth factor receptor 2 (KDR)

Synonyms

VEGFR2; VEGFR-2; VEGF-2 receptor; Protein-tyrosine kinase receptor flk-1; Kinase insert domain receptor; Fetal liver kinase 1; FLK1; FLK-1; CD309

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Gene Name

KDR

Target Type

Successful target

[1]

Disease

[+] 9 Target-related Diseases

Breast cancer [ICD-11: 2C60-2C6Y]

Colorectal cancer [ICD-11: 2B91]

Gastrointestinal stromal tumour [ICD-11: 2B5B]

Malignant digestive organ neoplasm [ICD-11: 2C11]

Renal cell carcinoma [ICD-11: 2C90]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Stomach cancer [ICD-11: 2B72]

Thrombocytopenia [ICD-11: 3B64]

Thyroid cancer [ICD-11: 2D10]

Function

Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.

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BioChemical Class

Kinase

UniProt ID

VGFR2_HUMAN

EC Number

EC 2.7.10.1

Sequence

MQSKVLLAVALWLCVETRAASVGLPSVSLDLPRLSIQKDILTIKANTTLQITCRGQRDLD
WLWPNNQSGSEQRVEVTECSDGLFCKTLTIPKVIGNDTGAYKCFYRETDLASVIYVYVQD
YRSPFIASVSDQHGVVYITENKNKTVVIPCLGSISNLNVSLCARYPEKRFVPDGNRISWD
SKKGFTIPSYMISYAGMVFCEAKINDESYQSIMYIVVVVGYRIYDVVLSPSHGIELSVGE
KLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRS
DQGLYTCAASSGLMTKKNSTFVRVHEKPFVAFGSGMESLVEATVGERVRIPAKYLGYPPP
EIKWYKNGIPLESNHTIKAGHVLTIMEVSERDTGNYTVILTNPISKEKQSHVVSLVVYVP
PQIGEKSLISPVDSYQYGTTQTLTCTVYAIPPPHHIHWYWQLEEECANEPSQAVSVTNPY
PCEEWRSVEDFQGGNKIEVNKNQFALIEGKNKTVSTLVIQAANVSALYKCEAVNKVGRGE
RVISFHVTRGPEITLQPDMQPTEQESVSLWCTADRSTFENLTWYKLGPQPLPIHVGELPT
PVCKNLDTLWKLNATMFSNSTNDILIMELKNASLQDQGDYVCLAQDRKTKKRHCVVRQLT
VLERVAPTITGNLENQTTSIGESIEVSCTASGNPPPQIMWFKDNETLVEDSGIVLKDGNR
NLTIRRVRKEDEGLYTCQACSVLGCAKVEAFFIIEGAQEKTNLEIIILVGTAVIAMFFWL
LLVIILRTVKRANGGELKTGYLSIVMDPDELPLDEHCERLPYDASKWEFPRDRLKLGKPL
GRGAFGQVIEADAFGIDKTATCRTVAVKMLKEGATHSEHRALMSELKILIHIGHHLNVVN
LLGACTKPGGPLMVIVEFCKFGNLSTYLRSKRNEFVPYKTKGARFRQGKDYVGAIPVDLK
RRLDSITSSQSSASSGFVEEKSLSDVEEEEAPEDLYKDFLTLEHLICYSFQVAKGMEFLA
SRKCIHRDLAARNILLSEKNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFDR
VYTIQSDVWSFGVLLWEIFSLGASPYPGVKIDEEFCRRLKEGTRMRAPDYTTPEMYQTML
DCWHGEPSQRPTFSELVEHLGNLLQANAQQDGKDYIVLPISETLSMEEDSGLSLPTSPVS
CMEEEEVCDPKFHYDNTAGISQYLQNSKRKSRPVSVKTFEDIPLEEPEVKVIPDDNQTDS
GMVLASEELKTLEDRTKLSPSFGGMVPSKSRESVASEGSNQTSGYQSGYHSDDTDTTVYS
SEEAELLKLIEIGVQTGSTAQILQPDSGTTLSSPPV

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

ADReCS ID

BADD_A04520

HIT2.0 ID

T04MBA

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 12 Approved Drugs

Axitinib

Drug Info

Approved

Renal cell carcinoma

[2], [3], [4]

Cabozantinib

Drug Info

Approved

Thyroid cancer

[5], [6]

Lenvatinib

Drug Info

Approved

Thyroid cancer

[7]

Pazopanib HCl

Drug Info

Approved

Renal cell carcinoma

[8]

Ramucirumab

Drug Info

Approved

Gastric adenocarcinoma

[9], [10]

Regorafenib

Drug Info

Approved

Metastatic colorectal cancer

[11], [3]

Romiplostim

Drug Info

Approved

Thrombocytopenia

[12], [13]

Sorafenib

Drug Info

Approved

Renal cell carcinoma

[14], [15]

Sunitinib

Drug Info

Approved

Gastrointestinal stromal tumour

[16]

Tivozanib

Drug Info

Approved

Renal cell carcinoma

[17]

Vandetanib

Drug Info

Approved

Solid tumour/cancer

[18], [19]

YN-968D1

Drug Info

Approved

Breast cancer

[20], [21], [22]

Clinical Trial Drug(s)

[+] 35 Clinical Trial Drugs

Brivanib

Drug Info

Phase 3

Liver cancer

[23], [24]

Cediranib

Drug Info

Phase 3

Peritoneal cavity cancer

[25], [26]

E-3810

Drug Info

Phase 3

Solid tumour/cancer

[27], [28]

HKI-272

Drug Info

Phase 3

Breast cancer

[29], [30]

Rivoceranib

Drug Info

Phase 3

Gastric adenocarcinoma

[30]

Rosiglitazone + metformin

Drug Info

Phase 3

Diabetic complication

[31]

Sulfatinib

Drug Info

Phase 3

Neuroendocrine cancer

[32]

MGCD516

Drug Info

Phase 2/3

Solid tumour/cancer

[33]

Alacizumab pegol

Drug Info

Phase 2

Non-small-cell lung cancer

[34]

BAY-57-9352

Drug Info

Phase 2

Solid tumour/cancer

[35]

BMS-690514

Drug Info

Phase 2

Chronic pain

[36]

CP-547632

Drug Info

Phase 2

Solid tumour/cancer

[37], [38]

Delphinidin

Drug Info

Phase 2

Cardiovascular disease

[39]

Famitinib

Drug Info

Phase 2

Solid tumour/cancer

[40], [41]

L-DOS47

Drug Info

Phase 2

Non-small-cell lung cancer

[30], [42]

RAF265

Drug Info

Phase 2

Melanoma

[43], [44]

TTAC-0001

Drug Info

Phase 2

Recurrent glioblastoma

[45]

VATALANIB

Drug Info

Phase 2

Solid tumour/cancer

[46], [47]

XL880

Drug Info

Phase 2

Squamous head and neck cell carcinom

[48], [49]

Anti-VEGFR2 CD8 cell therapy

Drug Info

Phase 1/2

Solid tumour/cancer

[50]

Elpamotide

Drug Info

Phase 1/2

Biliary cancer

[51]

MK-2461

Drug Info

Phase 1/2

Alzheimer disease

[52]

OTSGC-A24

Drug Info

Phase 1/2

Colorectal cancer

[53]

A168

Drug Info

Phase 1

Gastric adenocarcinoma

[54]

Altiratinib

Drug Info

Phase 1

Solid tumour/cancer

[55]

CEP-11981

Drug Info

Phase 1

Solid tumour/cancer

[56], [57]

CYC116

Drug Info

Phase 1

Solid tumour/cancer

[58]

E-7050

Drug Info

Phase 1

Head and neck cancer

[59], [60]

KRN633

Drug Info

Phase 1

Solid tumour/cancer

[61], [62]

OSI-930

Drug Info

Phase 1

Solid tumour/cancer

[63], [64]

Pegdinetanib

Drug Info

Phase 1

Non-small-cell lung cancer

[65]

PF-00337210

Drug Info

Phase 1

Solid tumour/cancer

[66]

PLX-4720

Drug Info

Phase 1

Cutaneous melanoma

[67]

TAK-593

Drug Info

Phase 1

Solid tumour/cancer

[68]

XL999

Drug Info

Phase 1

Advanced malignancy

[69]

Patented Agent(s)

[+] 1 Patented Agents

Antibodie derivative 10

Drug Info

Patented

Neoplasm

[70], [71]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

Motesanib

Drug Info

Discontinued in Phase 3

Non-small-cell lung cancer

[72], [73]

SU-14813

Drug Info

Discontinued in Phase 2

Breast cancer

[74], [75]

IMC-1C11

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[76]

CEP-5214

Drug Info

Terminated

Solid tumour/cancer

[77]

Mode of Action

[+] 4 Modes of Action

Modulator

[+] 17 Modulator drugs

Axitinib

Drug Info

[3], [4]

Ramucirumab

Drug Info

[10]

Regorafenib

Drug Info

[79]

Sorafenib

Drug Info

[15], [81]

Sunitinib

Drug Info

[82], [83]

Tivozanib

Drug Info

[17]

Brivanib

Drug Info

[87]

Delphinidin

Drug Info

[39]

RAF265

Drug Info

[97]

XL880

Drug Info

[87]

Anti-VEGFR2 CD8 cell therapy

Drug Info

[50], [98]

E-7050

Drug Info

[103]

OSI-930

Drug Info

[63], [64]

Pegdinetanib

Drug Info

[92]

PF-00337210

Drug Info

[104]

TAK-593

Drug Info

[68], [105]

EPI-0030

Drug Info

[92]

Inhibitor

[+] 103 Inhibitor drugs

Cabozantinib

Drug Info

[6], [78]

Lenvatinib

Drug Info

[1]

Pazopanib HCl

Drug Info

[8]

Romiplostim

Drug Info

[80]

Vandetanib

Drug Info

[84], [85]

YN-968D1

Drug Info

[86]

Cediranib

Drug Info

[84], [85]

E-3810

Drug Info

[88]

HKI-272

Drug Info

[89]

Rosiglitazone + metformin

Drug Info

[84], [90]

Sulfatinib

Drug Info

[91]

MGCD516

Drug Info

[92]

BAY-57-9352

Drug Info

[84]

BMS-690514

Drug Info

[94]

CP-547632

Drug Info

[84], [95]

Famitinib

Drug Info

[41]

VATALANIB

Drug Info

[89]

MK-2461

Drug Info

[52]

CEP-11981

Drug Info

[84]

CYC116

Drug Info

[102]

KRN633

Drug Info

[84]

PLX-4720

Drug Info

[83]

XL999

Drug Info

[106]

Pyridine derivative 18

Drug Info

[107]

Pyrimidine derivative 12

Drug Info

[70]

Pyrimidine derivative 13

Drug Info

[70]

Pyrimidine derivative 14

Drug Info

[70]

Pyrimidine derivative 4

Drug Info

[70]

Quinazoline derivative 15

Drug Info

[107]

Quinazoline derivative 16

Drug Info

[107]

Quinoline and quinazoline derivative 1

Drug Info

[70]

Motesanib

Drug Info

[108], [109], [110]

SU-14813

Drug Info

[84], [111], [112]

AG1295

Drug Info

[114]

(2-Methoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine

Drug Info

[116]

(3-Phenoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine

Drug Info

[116]

(4-Phenoxy-phenyl)-quinazolin-4-yl-amine

Drug Info

[117]

(5-Phenyl-oxazol-2-yl)-m-tolyl-amine

Drug Info

[116]

2-(1H-indazol-3-yl)-1H-benzo[d]imidazole

Drug Info

[118]

2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile

Drug Info

[116]

2-(p-toluidino)-4-phenylpyrimidine-5-carbonitrile

Drug Info

[119]

2-(pyrimidin-4-ylamino)thiazole-5-carbonitrile

Drug Info

[120]

3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione

Drug Info

[121]

3,4-diphenyl-1H-pyrrole-2,5-dione

Drug Info

[121]

3,6-Di-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine

Drug Info

[122]

3-((3-bromothiophen-2-yl)methylene)indolin-2-one

Drug Info

[123]

3-(1H-Indol-2-yl)-1H-quinolin-2-one

Drug Info

[124]

3-(4-aminophenyl)thieno[3,2-c]pyridin-4-amine

Drug Info

[125]

3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione

Drug Info

[121]

3-(5-Phenyl-oxazol-2-ylamino)-benzonitrile

Drug Info

[116]

3-(5-Thiophen-3-yl-pyridin-3-yl)-1H-indole

Drug Info

[126]

3-Benzimidazol-2-ylhydroquinolin-2-one

Drug Info

[127]

3-methyl-1H-thieno[2,3-c]pyrazole-5-carboxamide

Drug Info

[128]

3-phenyl-1,4-dihydroindeno[1,2-c]pyrazole

Drug Info

[129]

4-(4-aminophenyl)-1H-indazol-3yl-amine

Drug Info

[130]

4-(4-m-Tolylamino-phthalazin-1-yl)-benzamide

Drug Info

[131]

4-(4-p-Tolylamino-phthalazin-1-yl)-benzamide

Drug Info

[131]

4-(5-Phenyl-oxazol-2-ylamino)-benzenesulfonamide

Drug Info

[116]

4-(isoquinolin-5-yl)-N-m-tolylphthalazin-1-amine

Drug Info

[132]

4-(isoquinolin-5-yl)-N-o-tolylphthalazin-1-amine

Drug Info

[132]

4-Chloro-N-(2-chloro-benzoyl)-benzenesulfonamide

Drug Info

[133]

4-Chloro-N-(2-methyl-benzoyl)-benzenesulfonamide

Drug Info

[133]

4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide

Drug Info

[133]

4-Chloro-N-(4-chloro-benzoyl)-benzenesulfonamide

Drug Info

[133]

4-Chloro-N-(4-nitro-benzoyl)-benzenesulfonamide

Drug Info

[133]

4-phenyl-2-(phenylamino)pyrimidine-5-carbonitrile

Drug Info

[119]

4-[3-Hydroxyanilino]-6,7-Dimethoxyquinazoline

Drug Info

[123]

5-(4-Methoxy-phenyl)-1-phenyl-1H-benzoimidazole

Drug Info

[134]

6-(1H-Benzoimidazol-2-yl)-benzocyclohepten-7-one

Drug Info

[124]

6-o-tolylquinazolin-2-amine

Drug Info

[135]

8-methyl-4H,7H-indolo[6,5,4-cd]indol-5-one

Drug Info

[123]

AAL-993

Drug Info

[80]

AG-E-85378

Drug Info

[136]

AMG-429

Drug Info

[92]

AST-487

Drug Info

[137]

BIBF-1202

Drug Info

[138]

BMS-536924

Drug Info

[139]

BMS-645737

Drug Info

[140]

BX-795

Drug Info

[141]

BX-912

Drug Info

[141]

CB-676475

Drug Info

[142]

CEP-5104

Drug Info

[143]

IM-023911

Drug Info

[131]

IM-094261

Drug Info

[131]

IM-094882

Drug Info

[132]

Indolin-2-one deriv. 4b

Drug Info

[144]

Isoindolinone Urea derivative

Drug Info

[145]

JNJ-38158471

Drug Info

[92]

K-252a analogue

Drug Info

[146]

Ki-20227

Drug Info

[147]

L000021649

Drug Info

[122]

N-(2,4-Dichloro-benzoyl)-benzenesulfonamide

Drug Info

[133]

N-(3-Bromo-benzoyl)-4-chloro-benzenesulfonamide

Drug Info

[133]

Phenyl-(5-phenyl-oxazol-2-yl)-amine

Drug Info

[116]

PMID22765894C8h

Drug Info

[148]

PMID23639540C13a

Drug Info

[149]

PP121

Drug Info

[150]

Pyrazolo[1,5-a]pyrimidine 3G

Drug Info

[122]

Ro-4396686

Drug Info

[151]

100

SU-11652

Drug Info

[152]

101

TG-100435

Drug Info

[153]

102

VEGF receptor 2 kinase inhibitor I

Drug Info

[154]

103

[3-(5-Phenyl-oxazol-2-ylamino)-phenyl]-methanol

Drug Info

[116]

Antagonist

[+] 3 Antagonist drugs

Rivoceranib

Drug Info

[30]

Altiratinib

Drug Info

[101]

CEP-5214

Drug Info

[115]

Binder

[+] 1 Binder drugs

Antibodie derivative 6

Drug Info

[70]

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: Tivozanib

Ligand Info

Structure Description

CRYSTAL STRUCTURE OF VEGFR2 (JUXTAMEMBRANE AND KINASE DOMAINS) IN COMPLEX WITH TIVOZANIB (AV-951)

PDB:4ASE

Method

X-ray diffraction

Resolution

1.83 Å

Mutation

Yes

[155]

PDB Sequence

DPDELPLDEH

⁸¹⁶

CERLPYDASK

⁸²⁶

WEFPRDRLKL

⁸³⁶

GKPLGRGAFG

⁸⁴⁶

QVIEADAFGI

⁸⁵⁶

DKTATCRTVA

⁸⁶⁶

VKMLKEGATH

⁸⁷⁶

SEHRALMSEL

⁸⁸⁶

KILIHIGHHL

⁸⁹⁶

NVVNLLGACT

⁹⁰⁶

KPGGPLMVIV

⁹¹⁶

EFCKFGNLST

⁹²⁶

YLRSKRNEFV

⁹³⁶

PYKYKDFLTL

¹⁰⁰²

EHLICYSFQV

¹⁰¹²

AKGMEFLASR

¹⁰²²

KCIHRDLAAR

¹⁰³²

NILLSEKNVV

¹⁰⁴²

KICDFGLARD

¹⁰⁵²

IYKDPDYVRK

¹⁰⁶²

GDARLPLKWM

¹⁰⁷²

APETIFDRVY

¹⁰⁸²

TIQSDVWSFG

¹⁰⁹²

VLLWEIFSLG

¹¹⁰²

ASPYPGVKID

¹¹¹²

EEFCRRLKEG

¹¹²²

TRMRAPDYTT

¹¹³²

PEMYQTMLDC

¹¹⁴²

WHGEPSQRPT

¹¹⁵²

FSELVEHLGN

¹¹⁶²

LLQANAQ

Residue

Distance (Å)

LEU840

3.427

GLY841

3.790

VAL848

3.519

ALA866

3.470

LYS868

3.465

GLU885

2.985

ILE888

4.514

LEU889

3.626

ILE892

4.295

VAL898

4.676

VAL899

3.313

VAL914

3.991

VAL916

3.519

Residue

Distance (Å)

GLU917

3.086

PHE918

3.761

CYS919

2.851

LYS920

3.553

PHE921

4.703

GLY922

3.958

LEU1019

4.246

HIS1026

4.657

LEU1035

3.465

ILE1044

4.721

CYS1045

3.358

ASP1046

2.863

PHE1047

3.617

Ligand Name: Sunitinib

Ligand Info

Structure Description

CRYSTAL STRUCTURE OF VEGFR2 (JUXTAMEMBRANE AND KINASE DOMAINS) IN COMPLEX WITH SUNITINIB (SU11248) (N-2-diethylaminoethyl)-5-((Z)-(5- fluoro-2-oxo-1H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3- carboxamide)

PDB:4AGD

Method

X-ray diffraction

Resolution

2.81 Å

Mutation

Yes

[155]

PDB Sequence

LSIVMDPDEL

⁸¹¹

PLPYDASKWE

⁸²⁸

FPRDRLKLGK

⁸³⁸

PLGRGAFGQV

⁸⁴⁸

IEADAFGIDK

⁸⁵⁸

TATCRTVAVK

⁸⁶⁸

MLKEGATHSE

⁸⁷⁸

HRALMSELKI

⁸⁸⁸

LIHIGHHLNV

⁸⁹⁸

VNLLGACTKP

⁹⁰⁸

GGPLMVIVEF

⁹¹⁸

CKFGNLSTYL

⁹²⁸

RSKRNEFVPY

⁹³⁸

YKDFLTLEHL

¹⁰⁰⁵

ICYSFQVAKG

¹⁰¹⁵

MEFLASRKCI

¹⁰²⁵

HRDLAARNIL

¹⁰³⁵

LSEKNVVKIC

¹⁰⁴⁵

DFGLARDIYK

¹⁰⁵⁵

DPDYVRKGDA

¹⁰⁶⁵

RLPLKWMAPE

¹⁰⁷⁵

TIFDRVYTIQ

¹⁰⁸⁵

SDVWSFGVLL

¹⁰⁹⁵

WEIFSLGASP

¹¹⁰⁵

YPGVKIDEEF

¹¹¹⁵

CRRLKEGTRM

¹¹²⁵

RAPDYTTPEM

¹¹³⁵

YQTMLDCWHG

¹¹⁴⁵

EPSQRPTFSE

¹¹⁵⁵

LVEHLGNLLQ

¹¹⁶⁵

ANAQ

Residue

Distance (Å)

LYS838

4.310

LEU840

3.442

GLY841

4.330

VAL848

4.032

ALA866

3.540

LYS868

3.017

VAL899

3.752

VAL916

3.489

GLU917

2.932

Residue

Distance (Å)

PHE918

3.656

CYS919

2.922

LYS920

3.600

PHE921

4.491

GLY922

3.741

LEU1035

3.387

CYS1045

3.963

ASP1046

3.096

PHE1047

3.225

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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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). 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 Tissue Distribution 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 Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

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 Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Titin (TTN)		24.248 (121/499)	4.67E-20
Mixed lineage kinase 1 (MAP3K9)	PF00069 ; PF14604	33.880 (62/183)	1.70E-19
Serine/threonine-protein kinase 24 (STK24)	PF00069	34.228 (51/149)	1.12E-15
NIMA-related kinase 7 (NEK7)	PF00069	29.126 (60/206)	2.23E-15
Cyclin-dependent kinase-like 2 (CDKL2)	PF00069	27.817 (79/284)	2.54E-15
Serine/threonine-protein kinase 26 (STK26)	PF00069	34.000 (51/150)	3.13E-15
Oxidative stress responsive 1 (OXSR1)	PF12202 ; PF00069	33.333 (54/162)	4.15E-14
ERK activator kinase 5 (MAP2K5)	PF00564 ; PF00069	28.916 (48/166)	7.01E-14
Serine/threonine-protein kinase 25 (STK25)	PF00069	31.544 (47/149)	2.53E-13
Extracellular signal-regulated kinase 2 (ERK2)	PF00069	32.515 (53/163)	2.85E-13
Cyclin-dependent kinase 5 (CDK5)	PF00069	29.885 (52/174)	3.08E-13
Tyrosine-protein kinase EIF2AK2 (p68)	PF00035 ; PF00069	30.000 (45/150)	7.10E-13
Ste-20-related kinase (STK39)	PF12202 ; PF00069	33.540 (54/161)	7.77E-13
Protein kinase C delta (PRKCD)	PF00130 ; PF00069 ; PF00433 More >>	32.692 (51/156)	8.55E-13
Fused homolog (STK36)	PF13646 ; PF00069	29.530 (44/149)	9.18E-13
Ribosomal protein S6 kinase alpha-3 (RSK3)	PF00069 ; PF00433	30.719 (47/153)	1.01E-12
NIMA-related kinase 6 (NEK6)	PF00069	28.495 (53/186)	1.25E-12
Serine/threonine-protein kinase Nek8 (NEK8)	PF00069 ; PF00415	28.205 (55/195)	2.12E-12
Serine/threonine-protein kinase Nek9 (NEK9)	PF00069 ; PF00415	25.949 (41/158)	2.42E-12
PAK-1 protein kinase (PAK1)	PF00786 ; PF00069	29.801 (45/151)	2.96E-12
Aurora kinase A (AURKA)	PF00069	28.947 (44/152)	7.87E-12
Polo-like kinase 1 (PLK1)	PF00069 ; PF00659	29.333 (44/150)	8.25E-12
PAK-2 protein kinase (PAK2)	PF00786 ; PF00069	28.477 (43/151)	8.84E-12
Myosin-IIIa (MYO3A)	PF00612 ; PF00063 ; PF00069 More >>	31.500 (63/200)	9.97E-12
Extracellular signal-regulated kinase 1 (ERK1)	PF00069	34.783 (40/115)	1.29E-11
Ribosomal protein S6 kinase alpha-2 (RSK2)	PF00069 ; PF00433	30.263 (46/152)	1.65E-11
Serine/threonine-protein kinase PAK 3 (PAK3)	PF00786 ; PF00069	29.139 (44/151)	1.83E-11
Protein kinase C beta (PRKCB)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	33.607 (41/122)	1.95E-11
Serine/threonine-protein kinase Nek4 (NEK4)	PF00069	24.561 (42/171)	2.15E-11
Ribosomal protein S6 kinase alpha-1 (RSK1)	PF00069 ; PF00433	28.758 (44/153)	2.18E-11
Serine/threonine-protein kinase 3 (STK3)	PF11629 ; PF00069	31.293 (46/147)	2.84E-11
NIMA-related kinase 2 (NEK2)	PF00069	31.111 (42/135)	3.01E-11
Protein kinase C theta (PRKCQ)	PF00130 ; PF00069 ; PF00433 More >>	35.156 (45/128)	3.19E-11
MST-1 protein kinase (STK4)	PF11629 ; PF00069	31.293 (46/147)	3.58E-11
Serine/threonine-protein kinase MAK (MAK)	PF00069	27.374 (49/179)	3.77E-11
ERK activator kinase 7 (MAP2K7)	PF00069	28.846 (45/156)	4.21E-11
Cyclin-dependent kinase 6 (CDK6)	PF00069	33.333 (39/117)	5.34E-11
Cyclin-dependent kinase 3 (CDK3)	PF00069	36.522 (42/115)	5.80E-11
Cyclin-dependent kinase 7 (CDK7)	PF00069	35.294 (36/102)	6.29E-11
Unc-51 like kinase 3 (ULK3)	PF04212 ; PF00069	31.210 (49/157)	6.41E-11
Serine/threonine-protein kinase PAK 5 (PAK5)	PF00786 ; PF00069	30.675 (50/163)	6.62E-11
Cyclin-dependent kinase-like 3 (CDKL3)	PF00069	34.783 (40/115)	7.37E-11
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	PF00069	31.081 (46/148)	9.29E-11
Proto-oncogene serine/threonine-protein kinase mos (MOS)	PF00069	28.161 (49/174)	9.76E-11
Cyclin-dependent kinase-like 1 (CDKL1)	PF00069	26.842 (51/190)	1.05E-10
Serine/threonine-protein kinase PAK 6 (PAK6)	PF00786 ; PF00069	28.395 (46/162)	1.37E-10
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	PF00069 ; PF12721	27.723 (56/202)	1.43E-10
STE20-related serine/threonine-protein kinase (SLK)	PF00069 ; PF12474	25.448 (71/279)	1.58E-10
PRKR-like endoplasmic reticulum kinase (PERK)	PF00069	28.834 (47/163)	1.67E-10
TRAF2 and NCK interacting kinase (TNIK)	PF00780 ; PF00069	31.034 (54/174)	1.99E-10
Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3)	PF00069	27.485 (47/171)	2.16E-10
Cyclin-dependent kinase 17 (CDK17)	PF12330 ; PF00069	27.731 (33/119)	2.49E-10
Serine/threonine-protein kinase Nek5 (NEK5)	PF00069	24.260 (41/169)	3.07E-10
PAK-4 protein kinase (PAK4)	PF00786 ; PF00069	27.368 (52/190)	3.16E-10
Stress-activated protein kinase 2b (p38 beta)	PF00069	26.102 (77/295)	3.19E-10
Serine/threonine-protein kinase ULK2 (ULK2)	PF12063 ; PF00069	32.773 (39/119)	3.49E-10
Serine/threonine-protein kinase PLK3 (PLK3)	PF00069 ; PF00659	25.000 (38/152)	3.77E-10
Serine/threonine-protein kinase ICK (CILK1)	PF00069	34.259 (37/108)	3.95E-10
Extracellular signal-regulated kinase 5 (ERK5)	PF00069	33.333 (37/111)	4.23E-10
Salt-inducible kinase 2 (SIK2)	PF00069	29.012 (47/162)	4.29E-10
Cyclin-dependent kinase 1 (CDK1)	PF00069	26.190 (55/210)	5.30E-10
Protein kinase N1 (PKN1)	PF02185 ; PF00069 ; PF00433 More >>	30.049 (61/203)	6.01E-10
Cyclin-dependent kinase-like 5 (CDKL5)	PF00069	30.769 (36/117)	6.42E-10
Serine/threonine-protein kinase Nek11 (NEK11)	PF00069	25.146 (43/171)	7.60E-10
Cyclin-dependent kinase 20 (CDK20)	PF00069	34.862 (38/109)	9.68E-10
SPS1/STE20-related protein kinase YSK4 (YSK4)	PF00069	25.767 (42/163)	9.84E-10
Leucine-rich repeat kinase 2 (LRRK2)	PF16095 ; PF12799 ; PF13855 ; PF00069 ; PF08477 More >>	29.143 (51/175)	1.02E-09
MAPK/ERK kinase kinase 1 (MAP3K1)	PF00069	26.708 (43/161)	1.03E-09
Protein kinase C alpha (PRKCA)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	31.667 (38/120)	1.05E-09
Ribosomal protein S6 kinase alpha-6 (RSK6)	PF00069 ; PF00433	28.571 (50/175)	1.24E-09
TBC domain-containing protein kinase-like protein (TBCK)	PF00069 ; PF00566 ; PF00581 More >>	25.352 (54/213)	1.42E-09
MAPK/MAK/MRK overlapping kinase (MOK)	PF00069	32.432 (36/111)	1.49E-09
Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6)	PF00069	27.746 (48/173)	1.52E-09
Cyclin-dependent kinase 2 (CDK2)	PF00069	30.968 (48/155)	1.62E-09
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	PF16579 ; PF00069	26.768 (53/198)	1.62E-09
Cyclin-dependent kinase 12 (CDK12)	PF00069	32.323 (32/99)	1.66E-09
G protein-coupled receptor kinase 4 (GRK4)	PF00069 ; PF00615	31.452 (39/124)	1.70E-09
Glycogen synthase kinase-3 alpha (GSK-3A)	PF00069	28.723 (54/188)	1.84E-09
Death-associated protein kinase 2 (DAPK2)	PF00069	32.759 (38/116)	2.02E-09
Glycogen synthase kinase-3 beta (GSK-3B)	PF00069	28.191 (53/188)	2.06E-09
Protein kinase C gamma (PRKCG)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	32.787 (40/122)	2.07E-09
Polo-like kinase 2 (PLK2)	PF00069 ; PF00659	24.183 (37/153)	2.09E-09
Serine/threonine-protein kinase NLK (NLK)	PF00069	32.353 (33/102)	2.12E-09
Cyclin-dependent kinase 18 (CDK18)	PF00069	26.891 (32/119)	2.25E-09
Cyclin-dependent kinase 16 (CDK16)	PF12330 ; PF00069	26.050 (31/119)	3.14E-09
Cyclin-dependent kinase 13 (CDK13)	PF12330 ; PF00069	31.633 (31/98)	3.19E-09
Protein kinase G1 (PRKG1)	PF00027 ; PF16808 ; PF00069 More >>	30.392 (31/102)	3.24E-09
Serine/threonine-protein kinase ULK1 (ULK1)	PF12063 ; PF00069	35.238 (37/105)	3.28E-09
Misshapen-like kinase 1 (MINK1)	PF00780 ; PF00069	35.238 (37/105)	3.78E-09
Leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1)	PF12796 ; PF16095 ; PF00069 ; PF08477 More >>	26.804 (52/194)	3.90E-09
Serine/threonine-protein kinase 10 (STK10)	PF00069 ; PF12474	27.976 (47/168)	4.12E-09
BR serine/threonine kinase 1 (BRSK1)	PF00069	27.326 (47/172)	4.40E-09
cAMP-dependent protein kinase catalytic subunit gamma (PRKACG)	PF00069	31.068 (32/103)	4.64E-09
BR serine/threonine kinase 2 (BRSK2)	PF00069	27.168 (47/173)	4.67E-09
ERK activator kinase 1 (MEK1)	PF00069	33.000 (33/100)	5.11E-09
PKC-delta-interacting protein kinase (RIPK4)	PF12796 ; PF00069	29.221 (45/154)	5.47E-09
G protein-coupled receptor kinase 5 (GRK5)	PF00069 ; PF00615	33.028 (36/109)	5.62E-09
Calmodulin-dependent kinase II (CAMKK2)	PF00069	33.981 (35/103)	6.32E-09
Polo-like kinase 4 (PLK4)	PF00069 ; PF18190 ; PF18409 More >>	25.150 (42/167)	6.47E-09
ERK activator kinase 2 (MEK2)	PF00069	32.000 (32/100)	7.45E-09
Mitogen-activated protein kinase 15 (MAPK15)	PF00069	33.028 (36/109)	7.59E-09
Cyclin-dependent kinase 4 (CDK4)	PF00069	35.955 (32/89)	8.42E-09
Cytoplasmic DRAK1 (STK17A)	PF00069	34.259 (37/108)	9.06E-09
Cyclin-dependent kinase-like 4 (CDKL4)	PF00069	31.000 (31/100)	9.17E-09
Death-associated protein kinase 3 (DAPK3)	PF00069	30.400 (38/125)	9.95E-09
Stress-activated protein kinase 2a (p38 alpha)	PF00069	31.532 (35/111)	1.05E-08
Nik-related protein kinase (NRK)	PF00780 ; PF00069	27.322 (50/183)	1.05E-08
RAC-beta serine/threonine-protein kinase (AKT2)	PF00169 ; PF00069 ; PF00433 More >>	25.641 (50/195)	1.31E-08
5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)	PF16579 ; PF00069	26.000 (39/150)	1.34E-08
Putative 3-phosphoinositide-dependent protein kinase 2 (PDPK2P)	PF00069	27.273 (27/99)	1.45E-08
MAPK/ERK kinase kinase 4 (MAP3K4)	PF19431 ; PF00069	26.220 (43/164)	1.48E-08
G protein-coupled receptor kinase 6 (GRK6)	PF00069 ; PF00615	32.673 (33/101)	1.77E-08
Aurora kinase C (AURKC)	PF00069	32.174 (37/115)	2.00E-08
Phosphoinositide dependent protein kinase-1 (PDPK1)	PF14593 ; PF00069	27.273 (27/99)	2.12E-08
Mitogen-activated protein kinase kinase kinase 15 (MAP3K15)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	28.313 (47/166)	2.67E-08
cAMP-dependent protein kinase catalytic subunit alpha (PRKACA)	PF00069	30.000 (33/110)	3.11E-08
Death-associated protein kinase 1 (DAPK1)	PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF00069 More >>	32.000 (40/125)	3.39E-08
Mitogen-activated protein kinase 6 (MAPK6)	PF00069	33.043 (38/115)	3.54E-08
Protein kinase C iota (PRKCI)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	29.730 (33/111)	3.95E-08
TAO kinase 1 (TAOK1)	PF00069	29.139 (44/151)	4.21E-08
Ribosomal protein S6 kinase-related protein (RSKR)	PF00069	36.667 (33/90)	5.16E-08
cAMP-dependent protein kinase catalytic subunit beta (PRKACB)	PF00069	30.000 (33/110)	5.19E-08
NIMA-related kinase 1 (NEK1)	PF00069	27.273 (27/99)	5.43E-08
MEK kinase kinase 4 (MAP4K4)	PF00780 ; PF00069	34.862 (38/109)	5.65E-08
Mitogen-activated protein kinase 4 (MAPK4)	PF00069	35.849 (38/106)	6.00E-08
Ribosomal protein S6 kinase beta-1 (S6K1)	PF00069 ; PF00433	26.241 (37/141)	6.21E-08
Serine/threonine-protein kinase Nek3 (NEK3)	PF00069	24.699 (41/166)	6.25E-08
Cyclin-dependent kinase 14 (CDK14)	PF00069	27.642 (34/123)	6.27E-08
Myosin-IIIb (MYO3B)	PF00612 ; PF00063 ; PF00069 More >>	28.387 (44/155)	6.30E-08
Beta-adrenergic receptor kinase 1 (ADRBK1)	PF00169 ; PF00069 ; PF00615 More >>	31.538 (41/130)	6.73E-08
Protein kinase N2 (PKN2)	PF02185 ; PF00069 ; PF00433 More >>	29.448 (48/163)	6.74E-08
Hormonally up-regulated neu tumor-associated kinase (HUNK)	PF00069	33.010 (34/103)	8.54E-08
Serine/threonine-protein kinase TAO2 (TAOK2)	PF00069	33.333 (36/108)	9.53E-08
SIK family kinase 3 (SIK3)	PF00069	27.320 (53/194)	1.02E-07
CaM-kinase IV kinase (CAMKK1)	PF00069	34.579 (37/107)	1.11E-07
Putative serine/threonine-protein kinase PRKY (PRKY)	PF00069	30.693 (31/101)	1.11E-07
MAPK/ERK kinase kinase 3 (MAP3K3)	PF00564 ; PF00069	26.923 (42/156)	1.22E-07
Serine/threonine-protein kinase cot (COT)	PF00069	26.875 (43/160)	1.27E-07
cAMP-dependent protein kinase catalytic subunit PRKX (PRKX)	PF00069	30.693 (31/101)	1.45E-07
Rhodopsin kinase GRK1 (GRK1)	PF00069 ; PF00615	34.737 (33/95)	1.49E-07
Ribosomal protein S6 kinase beta-2 (RPS6KB2)	PF00069 ; PF00433	24.204 (38/157)	1.66E-07
Cyclin-dependent kinase 10 (CDK10)	PF00069	35.417 (34/96)	1.94E-07
Putative serine/threonine-protein kinase SIK1B (SIK1B)	PF00069	26.490 (40/151)	2.06E-07
Salt-inducible kinase 1 (SIK1)	PF00069	26.490 (40/151)	2.11E-07
Inhibitor of nuclear factor kappa-B kinase alpha (IKKA)	PF18397 ; PF12179 ; PF00069 More >>	32.673 (33/101)	2.74E-07
Beta-adrenergic receptor kinase 2 (ADRBK2)	PF00169 ; PF00069 ; PF00615 More >>	30.000 (39/130)	2.81E-07
Serine/threonine-protein kinase pim-2 (PIM2)	PF00069	24.675 (38/154)	3.06E-07
TAO kinase 3 (TAOK3)	PF00069	28.859 (43/149)	3.17E-07
Microtubule-associated serine/threonine-protein kinase 3 (MAST3)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	30.328 (37/122)	3.26E-07
Protein kinase G2 (PRKG2)	PF00027 ; PF00069	28.972 (31/107)	3.51E-07
Cyclin-dependent kinase 15 (CDK15)	PF00069	29.126 (30/103)	3.75E-07
Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1)	PF00069	28.402 (48/169)	3.89E-07
Myosin light chain kinase 3 (MYLK3)	PF00069	33.333 (38/114)	5.38E-07
Microtubule-associated serine/threonine-protein kinase 1 (MAST1)	PF08926 ; PF17820 ; PF00069 More >>	28.788 (38/132)	5.45E-07
Serine/threonine-protein kinase H2 (PSKH2)	PF00069	32.653 (32/98)	5.54E-07
Protein kinase N3 (PKN3)	PF02185 ; PF00069 ; PF00433 More >>	30.323 (47/155)	6.18E-07
Protein kinase C zeta (PRKCZ)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	28.829 (32/111)	6.84E-07
Microtubule-associated serine/threonine-protein kinase 2 (MAST2)	PF08926 ; PF17820 ; PF00069 More >>	28.030 (37/132)	7.03E-07
PDZ binding kinase (PBK)	PF00069	25.000 (53/212)	7.12E-07
Maternal embryonic leucine zipper kinase (MELK)	PF02149 ; PF00069	25.333 (38/150)	7.56E-07
RAC-alpha serine/threonine-protein kinase (AKT1)	PF00169 ; PF00069 ; PF00433 More >>	28.472 (41/144)	8.41E-07
Serine/threonine-protein kinase MARK2 (MARK2)	PF02149 ; PF00069 ; PF00627 More >>	27.333 (41/150)	8.61E-07
Serine/threonine-protein kinase PRP4 homolog (PRPF4B)	PF00069	31.818 (35/110)	9.94E-07
Serine/threonine-protein kinase 32A (STK32A)	PF00069	30.275 (33/109)	1.04E-06
MAP kinase signal-integrating kinase 2 (MKNK2)	PF00069	34.545 (38/110)	1.22E-06
Apoptosis signal-regulating kinase 1 (MAP3K5)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	25.641 (40/156)	1.31E-06
Protein kinase C eta type (PRKCH)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	27.119 (32/118)	1.32E-06
Myosin light chain kinase 2 (MYLK2)	PF00069	32.143 (36/112)	1.36E-06
RAC-gamma serine/threonine-protein kinase (AKT3)	PF00169 ; PF00069 ; PF00433 More >>	30.303 (30/99)	1.42E-06
Mitogen-activated protein kinase 13 (MAPK13)	PF00069	29.915 (35/117)	1.47E-06
NUAK family SNF1-like kinase 2 (NUAK2)	PF00069	33.333 (33/99)	1.53E-06
Serine/threonine-protein kinase 33 (STK33)	PF00069	29.808 (31/104)	1.57E-06
Testis-specific serine/threonine-protein kinase 6 (TSSK6)	PF00069	27.451 (42/153)	1.62E-06
Doublecortin-like kinase 1 (DCLK1)	PF03607 ; PF00069	31.193 (34/109)	1.66E-06
Adaptor-associated kinase 1 (AAK1)	PF00069	31.395 (27/86)	1.67E-06
Serine/threonine-protein kinase D2 (PRKD2)	PF00130 ; PF00069	30.081 (37/123)	1.70E-06
Protein kinase D (PRKD1)	PF00130 ; PF00169 ; PF00069 More >>	27.397 (40/146)	1.80E-06
Microtubule-associated serine/threonine-protein kinase 4 (MAST4)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	29.032 (36/124)	1.93E-06
Ribosomal protein S6 kinase alpha-5 (RSK5)	PF00069 ; PF00433	36.047 (31/86)	1.99E-06
Serine/threonine-protein kinase STK11 (STK11)	PF00069	25.641 (40/156)	2.10E-06
MEK kinase kinase 1 (MAP4K1)	PF00780 ; PF00069	31.579 (36/114)	2.16E-06
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	PF18397 ; PF12179 ; PF00069 More >>	30.693 (31/101)	2.35E-06
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	PF00069	27.097 (42/155)	2.59E-06
Serine/threonine-protein kinase NIK (MAP3K14)	PF00069	30.556 (33/108)	2.70E-06
MAP kinase p38 (MAPK12)	PF00069	31.429 (33/105)	2.75E-06
Cyclin-dependent kinase 9 (CDK9)	PF00069	22.776 (64/281)	2.97E-06
Ribosomal protein S6 kinase alpha-4 (RPS6KA4)	PF00069 ; PF00433	31.000 (31/100)	3.14E-06
Microtubule affinity regulating kinase 3 (MARK3)	PF02149 ; PF00069 ; PF00627 More >>	25.316 (40/158)	3.24E-06
Fc receptor-like protein 3 (FCRL3)	PF00047 ; PF13895	24.314 (62/255)	3.35E-06
PIM-3 protein kinase (PIM3)	PF00069	27.568 (51/185)	3.79E-06
Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)	PF08332 ; PF00069	31.081 (46/148)	3.93E-06
CDC-like kinase 1 (CLK1)	PF00069	25.497 (77/302)	4.02E-06
Serine/threonine-protein kinase pim-1 (PIM1)	PF00069	29.189 (54/185)	4.19E-06
Serine/threonine-protein kinase 32C (STK32C)	PF00069	32.692 (34/104)	4.70E-06
MAPK-activated protein kinase 2 (MAPKAPK2)	PF00069	25.287 (44/174)	5.12E-06
MAP/microtubule affinity-regulating kinase 4 (MARK4)	PF02149 ; PF00069 ; PF00627 More >>	24.684 (39/158)	5.13E-06
Calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B)	PF08332 ; PF00069	30.556 (44/144)	5.52E-06
Myosin light chain kinase family member 4 (MYLK4)	PF00069	33.333 (35/105)	5.71E-06
Serine/threonine-protein kinase ULK4 (ULK4)	PF00069	24.121 (48/199)	6.40E-06
Serine/threonine-protein kinase NIM1 (NIM1K)	PF00069	27.419 (34/124)	6.68E-06
Cyclin-dependent kinase 11B (CDK11B)	PF00069	32.292 (31/96)	6.75E-06
Cyclin-dependent kinase 11A (CDK11A)	PF00069	32.258 (30/93)	7.01E-06
Aurora kinase B (AURKB)	PF00069	22.581 (77/341)	7.09E-06
Protein kinase C epsilon (PRKCE)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	27.966 (33/118)	8.27E-06
Stress-activated protein kinase JNK2 (JNK2)	PF00069	33.333 (31/93)	8.83E-06
Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4)	PF12745 ; PF00069 ; PF05773 ; PF13393 More >>	27.225 (52/191)	8.95E-06
MAPK-activated protein kinase 3 (MAPKAPK3)	PF00069	25.466 (41/161)	9.16E-06
Serine/threonine-protein kinase Nek10 (NEK10)	PF00069	27.778 (30/108)	1.21E-05
Stress-activated protein kinase JNK3 (JNK3)	PF00069	33.333 (31/93)	1.29E-05
Serine/threonine-protein kinase D3 (PRKD3)	PF00130 ; PF00169 ; PF00069 More >>	27.397 (40/146)	1.41E-05
Omphalocele kinase 1 (NUAK1)	PF00069	27.632 (42/152)	1.42E-05
Serine/threonine-protein kinase SBK1 (SBK1)	PF00069	24.590 (45/183)	1.52E-05
Stress-activated protein kinase JNK1 (JNK1)	PF00069	33.333 (31/93)	1.77E-05
Cyclin-G-associated kinase (GAK)	PF00069 ; PF10409	23.656 (44/186)	1.85E-05
MAPK/ERK kinase kinase 2 (MAP3K2)	PF00564 ; PF00069	23.567 (37/157)	2.09E-05
Serine/threonine-protein kinase H1 (PSKH1)	PF00069	31.633 (31/98)	2.10E-05
Serine/threonine-protein kinase MARK1 (MARK1)	PF02149 ; PF00069 ; PF00627 More >>	28.000 (35/125)	2.60E-05
Doublecortin-like kinase 3 (DCLK3)	PF00069	25.688 (28/109)	2.62E-05
Rhodopsin kinase GRK7 (GRK7)	PF00069 ; PF00615	26.786 (30/112)	2.63E-05
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A)	PF08332 ; PF00069	29.730 (44/148)	2.85E-05
Calcium/calmodulin-dependent protein kinase type II subunit gamma (CAMK2G)	PF08332 ; PF00069	29.134 (37/127)	3.16E-05
Dual specificity protein kinase TTK (MPS1)	PF00069	24.324 (36/148)	3.43E-05
Serine/threonine-protein kinase Sgk2 (SGK2)	PF00069 ; PF00433	31.313 (31/99)	3.51E-05
Yet another novel kinase 2 (STK32B)	PF00069	33.654 (35/104)	3.87E-05
SNF-related serine/threonine-protein kinase (SNRK)	PF00069	22.286 (39/175)	4.03E-05
CDC-like kinase 4 (CLK4)	PF00069	24.820 (69/278)	4.18E-05
Carcinoembryonic antigen-related cell adhesion molecule 21 (CEACAM21)	PF00047 ; PF07686	25.146 (43/171)	4.50E-05
Homeodomain-interacting protein kinase 4 (HIPK4)	PF00069	31.304 (36/115)	4.90E-05
SCY1-like protein 2 (SCYL2)	PF00069	25.735 (35/136)	5.63E-05
Homeodomain-interacting protein kinase 3 (HIPK3)	PF00069	34.286 (36/105)	5.71E-05
Dual-specificity tyrosine-phosphorylation regulated kinase 4 (DYRK4)	PF00069	30.097 (31/103)	5.89E-05
Serine/threonine-protein kinase PDIK1L (PDIK1L)	PF00069	27.523 (30/109)	5.95E-05
Doublecortin-like kinase 2 (DCLK2)	PF03607 ; PF00069	28.713 (29/101)	5.97E-05
Casein kinase I gamma-1 (CSNK1G1)	PF12605 ; PF00069	26.154 (34/130)	6.09E-05
Homeodomain interacting protein kinase 2 (HIPK2)	PF00069	28.507 (63/221)	6.14E-05
Testis-specific serine kinase 2 (TSSK2)	PF00069	25.000 (40/160)	6.59E-05
Mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5)	PF00780 ; PF00069	31.915 (30/94)	6.86E-05
Bone morphogenetic protein receptor (BMPR2)	PF01064 ; PF00069	23.383 (47/201)	7.32E-05
Serine/threonine-protein kinase 35 (STK35)	PF00069	24.545 (27/110)	7.47E-05
MEK kinase kinase 3 (MAP4K3)	PF00780 ; PF00069	26.923 (49/182)	7.51E-05
BMP-2-inducible protein kinase (BMP2K)	PF15282 ; PF00069	33.735 (28/83)	8.01E-05
Serine/threonine-protein kinase Sgk3 (SGK3)	PF00069 ; PF00433 ; PF00787 More >>	29.310 (34/116)	8.90E-05
Cyclin-dependent kinase 8 (CDK8)	PF00069	30.928 (30/97)	9.40E-05
Homeodomain-interacting protein kinase 1 (HIPK1)	PF00069	34.286 (36/105)	9.80E-05
Sialic acid-binding Ig-like lectin 5 (SIGLEC5)	PF07686	33.333 (24/72)	1.09E-04
Casein kinase I gamma-3 (CSNK1G3)	PF12605 ; PF00069	26.207 (38/145)	1.13E-04
Fc receptor-like protein 5 (FCRL5)	PF13895	23.057 (89/386)	1.16E-04
Serine/threonine-protein kinase Sgk1 (SGK1)	PF00069 ; PF00433	27.273 (27/99)	1.21E-04
Apoptosis signal-regulating kinase 2 (MAP3K6)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	28.431 (29/102)	1.35E-04
Dual-specificity tyrosine-phosphorylation regulated kinase 3 (DYRK3)	PF00069	31.731 (33/104)	1.41E-04
Checkpoint kinase-1 (CHK1)	PF00069	33.696 (31/92)	1.63E-04
Endoplasmic reticulum to nucleus signaling 1 (ERN1)	PF00069 ; PF06479	30.081 (37/123)	2.00E-04
MEK kinase kinase 2 (MAP4K2)	PF00780 ; PF00069	28.025 (44/157)	2.25E-04
STE20-related kinase adapter protein beta (STRADB)	PF00069	24.167 (29/120)	2.31E-04
Cyclin-dependent kinase 19 (CDK19)	PF00069	30.928 (30/97)	2.32E-04
Testis-specific serine/threonine-protein kinase 4 (TSSK4)	PF00069	31.068 (32/103)	2.38E-04
Rho-associated protein kinase 1 (ROCK1)	PF00069 ; PF08912	30.097 (31/103)	2.42E-04
Anti-mullerian hormone II receptor (AMHR2)	PF00069	25.366 (52/205)	2.51E-04
Peripheral plasma membrane protein CASK (CASK)	PF00625 ; PF02828 ; PF00595 ; PF00069 ; PF00018 More >>	31.356 (37/118)	2.56E-04
Citron Rho-interacting kinase (CIT)	PF00780 ; PF00169 ; PF00069 More >>	30.769 (28/91)	2.90E-04
Serine/threonine-protein kinase 17B (STK17B)	PF00069	28.713 (29/101)	3.55E-04
TGF-beta receptor type I (TGFBR1)	PF01064 ; PF00069 ; PF08515 More >>	25.269 (47/186)	3.91E-04
Casein kinase I gamma-2 (CSNK1G2)	PF12605 ; PF00069	25.517 (37/145)	4.13E-04
Serine/threonine-protein kinase Kist (UHMK1)	PF00069 ; PF00076	32.653 (32/98)	4.37E-04
Activin receptor type IIA (ACVR2A)	PF01064 ; PF00069	24.737 (47/190)	4.49E-04
Activin receptor type IB (ACVR1B)	PF01064 ; PF00069 ; PF08515 More >>	25.134 (47/187)	4.65E-04
Calcium/calmodulin-dependent protein kinase type 1G (CAMK1G)	PF00069	26.957 (31/115)	4.71E-04
Casein kinase II alpha (CSNK2A1)	PF00069	25.510 (25/98)	7.32E-04
Serine/threonine kinase-like domain-containing protein STKLD1 (STKLD1)	PF00069	30.612 (30/98)	8.51E-04
Serine/threonine-protein kinase Chk2 (RAD53)	PF00498 ; PF00069	30.702 (35/114)	1.00E-03
Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)	PF00069 ; PF18394 ; PF18396 More >>	26.623 (41/154)	1.00E-03
NDR1 protein kinase (STK38)	PF00069 ; PF00433	24.828 (36/145)	1.00E-03
Fc receptor-like protein 2 (FCRL2)	PF13895	21.339 (51/239)	1.00E-03
Testis-specific serine/threonine-protein kinase 1 (TSSK1B)	PF00069	25.197 (32/127)	1.00E-03
Click to Show/Hide the Information of Human Similarity Proteins


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
MAPK signaling pathway	hsa04010	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Ras signaling pathway	hsa04014	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Rap1 signaling pathway	hsa04015	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Calcium signaling pathway	hsa04020	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
PI3K-Akt signaling pathway	hsa04151	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
VEGF signaling pathway	hsa04370	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Focal adhesion	hsa04510	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	46	Degree centrality	4.94E-03	Betweenness centrality	3.76E-03
Closeness centrality	2.61E-01	Radiality	1.45E+01	Clustering coefficient	1.46E-01
Neighborhood connectivity	4.49E+01	Topological coefficient	4.78E-02	Eccentricity	11
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 Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins 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

[+] 8 KEGG Pathways

Ras signaling pathway

Rap1 signaling pathway

Cytokine-cytokine receptor interaction

Endocytosis

PI3K-Akt signaling pathway

VEGF signaling pathway

Focal adhesion

Proteoglycans in cancer

NetPath Pathway

[+] 1 NetPath Pathways

IL2 Signaling Pathway

Panther Pathway

[+] 2 Panther Pathways

Angiogenesis

VEGF signaling pathway

PID Pathway

[+] 9 PID Pathways

HIF-2-alpha transcription factor network

Beta3 integrin cell surface interactions

Signaling events mediated by TCPTP

SHP2 signaling

S1P1 pathway

VEGF and VEGFR signaling network

Integrins in angiogenesis

Signaling events mediated by VEGFR1 and VEGFR2

Notch-mediated HES/HEY network

Reactome

[+] 6 Reactome Pathways

Neurophilin interactions with VEGF and VEGFR

VEGF binds to VEGFR leading to receptor dimerization

Integrin cell surface interactions

EPHA-mediated growth cone collapse

VEGFA-VEGFR2 Pathway

VEGFR2 mediated cell proliferation

WikiPathways

[+] 5 WikiPathways

Focal Adhesion

Nifedipine Activity

Cardiac Progenitor Differentiation

Signaling by VEGF

Angiogenesis

Target-Related Models and Studies

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Target Validation

Target Validation Info

Target QSAR Model

References

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ClinicalTrials.gov (NCT00875264) Open-Label Study to Determine the Maximum Tolerated Oral Dose of the Kinase Inhibitor CEP-11981 in Patients With Advanced Cancer. U.S. National Institutes of Health.

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OSI-930 analogues as novel reversal agents for ABCG2-mediated multidrug resistance. Biochem Pharmacol. 2012 Sep 15;84(6):766-74.

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