Target Information

Target General Information

Target ID

T40474 (Former ID: TTDC00110)

Target Name

Proto-oncogene c-Met (MET)

Synonyms

Tyrosine-protein kinase Met; Scatter factor receptor; SF receptor; Met proto-oncogene tyrosine kinase; Hepatocyte growth factor receptor; HGF/SF receptor; HGF-SF receptor; HGF receptor; C-met; C-Met receptor tyrosine kinase

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Gene Name

MET

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

Lung cancer [ICD-11: 2C25]

Non-small-cell lung cancer [ICD-11: 2C25]

Thyroid cancer [ICD-11: 2D10]

Function

Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.

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BioChemical Class

Kinase

UniProt ID

MET_HUMAN

EC Number

EC 2.7.10.1

Sequence

MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEH
HIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMAL
VVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSAL
GAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPE
FRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECIL
TEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRS
AMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEF
TTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFL
LDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGW
CHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKK
TRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVIT
SISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEF
AVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVH
EAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPV
FKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDL
LKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQ
IKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGS
CRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHF
NEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVL
SLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKF
VHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKF
TTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCW
HPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVD
TRPASFWETS

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T92AMR

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 5 Approved Drugs

Amivantamab

Drug Info

Approved

Non-small-cell lung cancer

[2]

Cabozantinib

Drug Info

Approved

Thyroid cancer

[3], [4]

Capmatinib

Drug Info

Approved

Non-small-cell lung cancer

[5]

Crizotinib

Drug Info

Approved

Non-small-cell lung cancer

[6], [7]

Tepotinib

Drug Info

Approved

Non-small-cell lung cancer

[8]

Clinical Trial Drug(s)

[+] 41 Clinical Trial Drugs

Beperminogene perplasmid

Drug Info

Phase 3

Heart disease

[9]

RG3638

Drug Info

Phase 3

Non-small-cell lung cancer

[10]

Savolitinib

Drug Info

Phase 3

Renal cell carcinoma

[11]

Tivantinib

Drug Info

Phase 3

Solid tumour/cancer

[12], [13]

MGCD516

Drug Info

Phase 2/3

Solid tumour/cancer

[14]

AMG 208

Drug Info

Phase 2

Solid tumour/cancer

[15]

AMG 337

Drug Info

Phase 2

Solid tumour/cancer

[16]

APL-101

Drug Info

Phase 2

Non-small-cell lung cancer

[17]

CMX-2043

Drug Info

Phase 2

Myocardial reperfusion injury

[18]

Emibetuzumab

Drug Info

Phase 2

Solid tumour/cancer

[19]

HM-5016504

Drug Info

Phase 2

Solid tumour/cancer

[20]

LY-2875358

Drug Info

Phase 2

Solid tumour/cancer

[21]

LY2801653

Drug Info

Phase 2

Solid tumour/cancer

[22]

SAR-125844

Drug Info

Phase 2

Solid tumour/cancer

[23]

Telisotuzumab vedotin

Drug Info

Phase 2

Non-small-cell lung cancer

[24]

XL880

Drug Info

Phase 2

Squamous head and neck cell carcinom

[25], [26]

Anti-C-met CAR-T cells

Drug Info

Phase 1/2

Colorectal cancer

[27]

ChronSeal

Drug Info

Phase 1/2

Fibrosis

[28]

MK-2461

Drug Info

Phase 1/2

Alzheimer disease

[29]

Sym015

Drug Info

Phase 1/2

Solid tumour/cancer

[11], [19]

ABBV-399

Drug Info

Phase 1

Solid tumour/cancer

[30]

ABT-700

Drug Info

Phase 1

Advanced solid tumour

[31]

Altiratinib

Drug Info

Phase 1

Solid tumour/cancer

[32]

Autologous T Cells Expressing MET scFv CAR

Drug Info

Phase 1

Melanoma

[33]

AZD9592

Drug Info

Phase 1

Aggressive cancer

[34]

BPI-9016 M

Drug Info

Phase 1

Solid tumour/cancer

[35]

C-Met/PD-L1 CAR-T Cell

Drug Info

Phase 1

Hepatocellular carcinoma

[36]

CBT-101

Drug Info

Phase 1

Solid tumour/cancer

[11]

E-7050

Drug Info

Phase 1

Head and neck cancer

[37], [38]

EMD-1204831

Drug Info

Phase 1

Solid tumour/cancer

[39]

Hepapoietin

Drug Info

Phase 1

Liver disease

[40]

JNJ-38877605

Drug Info

Phase 1

Solid tumour/cancer

[41]

LY3164530

Drug Info

Phase 1

Advanced cancer

[42]

MK-8033

Drug Info

Phase 1

Solid tumour/cancer

[43]

PF-4217903

Drug Info

Phase 1

Solid tumour/cancer

[44]

REGN5093

Drug Info

Phase 1

Non-small-cell lung cancer

[45]

RXDX-106

Drug Info

Phase 1

Solid tumour/cancer

[46]

SGX523

Drug Info

Phase 1

Solid tumour/cancer

[47], [48]

TPX-0022

Drug Info

Phase 1

Solid tumour/cancer

[49]

TR1801-ADC

Drug Info

Phase 1

Solid tumour/cancer

[50]

XL092

Drug Info

Phase 1

Solid tumour/cancer

[51]

Preclinical Drug(s)

[+] 2 Preclinical Drugs

Mteron-F1

Drug Info

Preclinical

Mucositis

[52]

NPS-1034

Drug Info

Preclinical

Solid tumour/cancer

[53]

Mode of Action

[+] 5 Modes of Action

Inhibitor

[+] 49 Inhibitor drugs

Amivantamab

Drug Info

[54]

Cabozantinib

Drug Info

[4], [55]

Savolitinib

Drug Info

[11]

Tivantinib

Drug Info

[12]

MGCD516

Drug Info

[57]

MGCD516

Drug Info

[58]

APL-101

Drug Info

[61]

Emibetuzumab

Drug Info

[19]

HM-5016504

Drug Info

[57]

SAR-125844

Drug Info

[67]

BMS-777607

Drug Info

[70]

ChronSeal

Drug Info

[71]

MK-2461

Drug Info

[29]

Sym015

Drug Info

[11]

ABBV-399

Drug Info

[19]

Altiratinib

Drug Info

[55], [73]

BPI-9016 M

Drug Info

[75]

CBT-101

Drug Info

[11]

EMD-1204831

Drug Info

[77]

Hepapoietin

Drug Info

[78]

JNJ-38877605

Drug Info

[79]

MK-8033

Drug Info

[81]

PF-4217903

Drug Info

[82]

REGN5093

Drug Info

[83]

RXDX-106

Drug Info

[84]

SGX523

Drug Info

[85]

TPX-0022

Drug Info

[86]

XL092

Drug Info

[88]

NPS-1034

Drug Info

[89]

1-(2-nitrophenethyl)-1H-pyrrolo[3,2-b]pyridine

Drug Info

[90]

1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine

Drug Info

[90]

1-benzyl-1H-pyrrolo[3,2-b]pyridine

Drug Info

[90]

3-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

Drug Info

[90]

AM7

Drug Info

[91]

Anti-cMET mab

Drug Info

[57]

APS-3010

Drug Info

[57]

BAY-85-3474

Drug Info

[57]

BMS-536924

Drug Info

[92]

CMET Avimer polypeptides

Drug Info

[57]

DP-3590

Drug Info

[57]

PF-00614435

Drug Info

[57]

PHA-665752

Drug Info

[57]

PMID21123062C27

Drug Info

[94]

PMID21967808CR-16

Drug Info

[95]

PMID24210504C1o

Drug Info

[96]

PRS-110

Drug Info

[57]

RP-1040

Drug Info

[57]

SU11274

Drug Info

[97]

TP-801

Drug Info

[57]

Modulator

[+] 14 Modulator drugs

Capmatinib

Drug Info

[5]

Crizotinib

Drug Info

[1]

Tepotinib

Drug Info

[8]

Beperminogene perplasmid

Drug Info

[56]

RG3638

Drug Info

[57]

AMG 208

Drug Info

[59]

AMG 337

Drug Info

[60]

CMX-2043

Drug Info

[62]

LY2801653

Drug Info

[65], [66]

XL880

Drug Info

[69]

ABT-700

Drug Info

[72]

E-7050

Drug Info

[76]

LY3164530

Drug Info

[80]

GE-137

Drug Info

[93]

CAR-T-Cell-Therapy

[+] 2 CAR-T-Cell-Therapy drugs

Anti-C-met CAR-T cells

Drug Info

[27]

Autologous T Cells Expressing MET scFv CAR

Drug Info

[33]

CAR-T-Cell-Therapy(Dual specific)

[+] 1 CAR-T-Cell-Therapy(Dual specific) drugs

C-Met/PD-L1 CAR-T Cell

Drug Info

[36]

Stimulator

[+] 1 Stimulator drugs

Mteron-F1

Drug Info

[52]

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: Adenosine triphosphate

Ligand Info

Structure Description

Structure of MET receptor tyrosine kinase in complex with ATP

PDB:3DKC

Method

X-ray diffraction

Resolution

1.52 Å

Mutation

Yes

[99]

PDB Sequence

VHIDLSALNP

¹⁰⁶⁰

ELVQAVQHVV

¹⁰⁷⁰

IGPSSLIVHF

¹⁰⁸⁰

NEVIGRGHFG

¹⁰⁹⁰

CVYHGTLLDN

¹¹⁰⁰

DGKKIHCAVK

¹¹¹⁰

SLNRITDIGE

¹¹²⁰

VSQFLTEGII

¹¹³⁰

MKDFSHPNVL

¹¹⁴⁰

SLLGICLRSE

¹¹⁵⁰

GSPLVVLPYM

¹¹⁶⁰

KHGDLRNFIR

¹¹⁷⁰

NETHNPTVKD

¹¹⁸⁰

LIGFGLQVAK

¹¹⁹⁰

GMKFLASKKF

¹²⁰⁰

VHRDLAARNC

¹²¹⁰

MLDEKFTVKV

¹²²⁰

ADFGLARDMY

¹²³⁰

DKEFDSVHNK

¹²⁴⁰

TGAKLPVKWM

¹²⁵⁰

ALESLQTQKF

¹²⁶⁰

TTKSDVWSFG

¹²⁷⁰

VLLWELMTRG

¹²⁸⁰

APPYPDVNTF

¹²⁹⁰

DITVYLLQGR

¹³⁰⁰

RLLQPEYCPD

¹³¹⁰

PLYEVMLKCW

¹³²⁰

HPKAEMRPSF

¹³³⁰

SELVSRISAI

¹³⁴⁰

FSTFIGEHYV

¹³⁵⁰

HVNATYVNVK

¹³⁶⁰

Residue

Distance (Å)

ILE1084

3.377

GLY1085

3.534

ARG1086

3.912

GLY1087

3.138

HIS1088

2.665

PHE1089

3.872

GLY1090

3.501

CYS1091

4.829

VAL1092

3.428

ALA1108

3.480

LYS1110

2.835

Residue

Distance (Å)

LEU1140

4.083

LEU1157

3.757

PRO1158

2.827

TYR1159

3.840

MET1160

2.980

ASP1164

4.021

ASP1204

2.565

ARG1208

2.859

ASN1209

2.924

MET1211

3.465

ASP1222

2.862

Ligand Name: Crizotinib

Ligand Info

Structure Description

X-ray Structure of PF-02341066 bound to the kinase domain of c-Met

PDB:2WGJ

Method

X-ray diffraction

Resolution

2.00 Å

Mutation

[100]

PDB Sequence

HIDLSALNPE

¹⁰⁶¹

LVQAVQHVVI

¹⁰⁷¹

GPSSLIVHFN

¹⁰⁸¹

EVIGRGHFGC

¹⁰⁹¹

VYHGTLLKKI

¹¹⁰⁵

HCAVKSLNRI

¹¹¹⁵

TDIGEVSQFL

¹¹²⁵

TEGIIMKDFS

¹¹³⁵

HPNVLSLLGI

¹¹⁴⁵

CLRSEGSPLV

¹¹⁵⁵

VLPYMKHGDL

¹¹⁶⁵

RNFIRNETHN

¹¹⁷⁵

PTVKDLIGFG

¹¹⁸⁵

LQVAKGMKYL

¹¹⁹⁵

ASKKFVHRDL

¹²⁰⁵

AARNCMLDEK

¹²¹⁵

FTVKVADFGL

¹²²⁵

ARDMYDKEYY

¹²³⁵

SVHNKTGAKL

¹²⁴⁵

PVKWMALESL

¹²⁵⁵

QTQKFTTKSD

¹²⁶⁵

VWSFGVLLWE

¹²⁷⁵

LMTRGAPPYP

¹²⁸⁵

DVNTFDITVY

¹²⁹⁵

LLQGRRLLQP

¹³⁰⁵

EYCPDPLYEV

¹³¹⁵

MLKCWHPKAE

¹³²⁵

MRPSFSELVS

¹³³⁵

RISAIFSTFI

¹³⁴⁵

Residue

Distance (Å)

ILE1084

3.465

GLY1085

3.681

VAL1092

3.762

ALA1108

3.265

LYS1110

4.690

LEU1140

3.848

LEU1157

3.692

PRO1158

3.051

TYR1159

3.435

MET1160

2.910

LYS1161

3.865

Residue

Distance (Å)

HIS1162

4.009

GLY1163

3.694

ARG1208

3.520

ASN1209

3.767

CYS1210

4.847

MET1211

3.386

ALA1221

3.469

ASP1222

3.359

ALA1226

4.050

TYR1230

3.461

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 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
Mixed lineage kinase 1 (MAP3K9)	PF00069 ; PF14604	30.325 (84/277)	6.48E-31
Serine/threonine-protein kinase 25 (STK25)	PF00069	26.642 (73/274)	5.92E-20
Serine/threonine-protein kinase 24 (STK24)	PF00069	27.907 (72/258)	3.13E-19
Serine/threonine-protein kinase 26 (STK26)	PF00069	28.014 (79/282)	3.39E-18
SPS1/STE20-related protein kinase YSK4 (YSK4)	PF00069	28.033 (67/239)	6.77E-18
Serine/threonine-protein kinase Nek10 (NEK10)	PF00069	26.073 (79/303)	1.77E-17
Putative serine/threonine-protein kinase PRKY (PRKY)	PF00069	28.182 (62/220)	2.21E-17
Serine/threonine-protein kinase Nek5 (NEK5)	PF00069	28.431 (58/204)	7.11E-17
PKC-delta-interacting protein kinase (RIPK4)	PF12796 ; PF00069	27.879 (92/330)	1.40E-16
Ribosomal protein S6 kinase alpha-1 (RSK1)	PF00069 ; PF00433	28.000 (63/225)	2.58E-16
cAMP-dependent protein kinase catalytic subunit PRKX (PRKX)	PF00069	27.727 (61/220)	3.21E-16
Fused homolog (STK36)	PF13646 ; PF00069	27.679 (62/224)	3.25E-16
Ribosomal protein S6 kinase alpha-3 (RSK3)	PF00069 ; PF00433	26.957 (62/230)	5.32E-16
NIMA-related kinase 7 (NEK7)	PF00069	25.856 (68/263)	6.76E-16
NIMA-related kinase 6 (NEK6)	PF00069	26.070 (67/257)	7.24E-16
Serine/threonine-protein kinase ULK2 (ULK2)	PF12063 ; PF00069	26.695 (63/236)	9.43E-16
Ribosomal protein S6 kinase alpha-2 (RSK2)	PF00069 ; PF00433	26.201 (60/229)	2.46E-15
Serine/threonine-protein kinase Sgk1 (SGK1)	PF00069 ; PF00433	25.902 (79/305)	3.09E-15
Myosin-IIIa (MYO3A)	PF00612 ; PF00063 ; PF00069 More >>	28.731 (77/268)	3.38E-15
MST-1 protein kinase (STK4)	PF11629 ; PF00069	25.475 (67/263)	6.08E-15
Serine/threonine-protein kinase 3 (STK3)	PF11629 ; PF00069	26.744 (69/258)	3.25E-14
Serine/threonine-protein kinase Nek4 (NEK4)	PF00069	25.484 (79/310)	5.97E-14
Cyclin-dependent kinase 2 (CDK2)	PF00069	29.064 (59/203)	6.52E-14
Protein kinase C delta (PRKCD)	PF00130 ; PF00069 ; PF00433 More >>	27.962 (59/211)	6.66E-14
IL-1 receptor-associated kinase 1 (IRAK1)	PF00531 ; PF00069	27.014 (57/211)	6.79E-14
Protein kinase C beta (PRKCB)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	29.245 (62/212)	7.08E-14
Serine/threonine-protein kinase ULK1 (ULK1)	PF12063 ; PF00069	28.169 (60/213)	7.49E-14
Protein kinase C alpha (PRKCA)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	27.488 (58/211)	1.33E-13
NIMA-related kinase 2 (NEK2)	PF00069	27.612 (74/268)	1.49E-13
Serine/threonine-protein kinase 32A (STK32A)	PF00069	30.342 (71/234)	1.54E-13
Unc-51 like kinase 3 (ULK3)	PF04212 ; PF00069	30.189 (64/212)	1.74E-13
Mitogen-activated protein kinase 15 (MAPK15)	PF00069	27.230 (58/213)	1.89E-13
Cyclin-dependent kinase 3 (CDK3)	PF00069	28.571 (58/203)	2.07E-13
Cyclin-dependent kinase 1 (CDK1)	PF00069	26.190 (55/210)	2.81E-13
Serine/threonine-protein kinase Nek3 (NEK3)	PF00069	25.373 (51/201)	2.99E-13
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	PF00069 ; PF12721	26.882 (75/279)	4.02E-13
Cyclin-dependent kinase 17 (CDK17)	PF12330 ; PF00069	27.907 (60/215)	4.14E-13
PAK-2 protein kinase (PAK2)	PF00786 ; PF00069	25.391 (65/256)	4.38E-13
Serine/threonine-protein kinase Nek11 (NEK11)	PF00069	23.810 (65/273)	4.82E-13
Microtubule affinity regulating kinase 3 (MARK3)	PF02149 ; PF00069 ; PF00627 More >>	25.221 (57/226)	4.83E-13
Cyclin-dependent kinase 16 (CDK16)	PF12330 ; PF00069	28.019 (58/207)	5.24E-13
Ribosomal protein S6 kinase beta-1 (S6K1)	PF00069 ; PF00433	25.822 (55/213)	5.45E-13
Serine/threonine-protein kinase MARK1 (MARK1)	PF02149 ; PF00069 ; PF00627 More >>	26.991 (61/226)	5.60E-13
RAC-gamma serine/threonine-protein kinase (AKT3)	PF00169 ; PF00069 ; PF00433 More >>	25.362 (70/276)	6.05E-13
MAPK/ERK kinase kinase 3 (MAP3K3)	PF00564 ; PF00069	27.103 (58/214)	8.54E-13
PAK-1 protein kinase (PAK1)	PF00786 ; PF00069	26.335 (74/281)	9.53E-13
Serine/threonine-protein kinase MARK2 (MARK2)	PF02149 ; PF00069 ; PF00627 More >>	27.354 (61/223)	9.68E-13
Aurora kinase A (AURKA)	PF00069	24.621 (65/264)	1.25E-12
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	PF18397 ; PF12179 ; PF00069 More >>	25.455 (56/220)	1.38E-12
Proto-oncogene serine/threonine-protein kinase mos (MOS)	PF00069	21.875 (63/288)	1.47E-12
Myosin light chain kinase family member 4 (MYLK4)	PF00069	26.407 (61/231)	1.61E-12
Cyclin-dependent kinase 6 (CDK6)	PF00069	28.638 (61/213)	1.75E-12
Leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1)	PF12796 ; PF16095 ; PF00069 ; PF08477 More >>	27.600 (69/250)	1.84E-12
Ste-20-related kinase (STK39)	PF12202 ; PF00069	28.755 (67/233)	1.90E-12
NUAK family SNF1-like kinase 2 (NUAK2)	PF00069	26.442 (55/208)	1.99E-12
Serine/threonine-protein kinase PAK 3 (PAK3)	PF00786 ; PF00069	26.335 (74/281)	2.10E-12
MAP/microtubule affinity-regulating kinase 4 (MARK4)	PF02149 ; PF00069 ; PF00627 More >>	25.333 (57/225)	2.15E-12
Ribosomal protein S6 kinase beta-2 (RPS6KB2)	PF00069 ; PF00433	24.900 (62/249)	2.55E-12
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	PF00069	26.316 (70/266)	2.82E-12
Oxidative stress responsive 1 (OXSR1)	PF12202 ; PF00069	26.335 (74/281)	3.25E-12
Polo-like kinase 4 (PLK4)	PF00069 ; PF18190 ; PF18409 More >>	26.267 (57/217)	3.26E-12
Protein kinase C theta (PRKCQ)	PF00130 ; PF00069 ; PF00433 More >>	25.306 (62/245)	3.71E-12
Maternal embryonic leucine zipper kinase (MELK)	PF02149 ; PF00069	25.217 (58/230)	3.76E-12
Salt-inducible kinase 2 (SIK2)	PF00069	25.000 (61/244)	3.91E-12
MAPK/ERK kinase kinase 2 (MAP3K2)	PF00564 ; PF00069	26.199 (71/271)	4.82E-12
Leucine-rich repeat kinase 2 (LRRK2)	PF16095 ; PF12799 ; PF13855 ; PF00069 ; PF08477 More >>	25.758 (68/264)	4.98E-12
Serine/threonine-protein kinase Nek9 (NEK9)	PF00069 ; PF00415	24.419 (63/258)	5.68E-12
Ribosomal protein S6 kinase alpha-6 (RSK6)	PF00069 ; PF00433	26.238 (53/202)	5.74E-12
Testis-specific serine kinase 2 (TSSK2)	PF00069	28.444 (64/225)	6.02E-12
Cyclin-dependent kinase 5 (CDK5)	PF00069	25.681 (66/257)	6.54E-12
Serine/threonine-protein kinase 33 (STK33)	PF00069	24.201 (53/219)	8.38E-12
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	PF16579 ; PF00069	29.858 (63/211)	9.23E-12
Omphalocele kinase 1 (NUAK1)	PF00069	25.871 (52/201)	9.43E-12
Serine/threonine-protein kinase D2 (PRKD2)	PF00130 ; PF00069	28.643 (57/199)	1.01E-11
Protein kinase D (PRKD1)	PF00130 ; PF00169 ; PF00069 More >>	24.138 (70/290)	1.25E-11
Stress-activated protein kinase 2a (p38 alpha)	PF00069	26.389 (57/216)	1.33E-11
TRAF2 and NCK interacting kinase (TNIK)	PF00780 ; PF00069	25.446 (57/224)	1.74E-11
Protein kinase C epsilon (PRKCE)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	27.602 (61/221)	1.82E-11
Serine/threonine-protein kinase D3 (PRKD3)	PF00130 ; PF00169 ; PF00069 More >>	25.490 (78/306)	1.99E-11
Myosin light chain kinase 3 (MYLK3)	PF00069	27.451 (56/204)	2.01E-11
Serine/threonine-protein kinase PAK 5 (PAK5)	PF00786 ; PF00069	26.293 (61/232)	2.35E-11
RAC-beta serine/threonine-protein kinase (AKT2)	PF00169 ; PF00069 ; PF00433 More >>	26.341 (54/205)	2.54E-11
Inhibitor of nuclear factor kappa-B kinase alpha (IKKA)	PF18397 ; PF12179 ; PF00069 More >>	26.147 (57/218)	2.87E-11
PDZ binding kinase (PBK)	PF00069	26.738 (50/187)	3.20E-11
TGF-beta-stimulated factor 1 (STK16)	PF00069	23.140 (56/242)	3.21E-11
Cyclin-dependent kinase 7 (CDK7)	PF00069	26.442 (55/208)	3.22E-11
Hormonally up-regulated neu tumor-associated kinase (HUNK)	PF00069	26.756 (80/299)	3.38E-11
Cyclin-dependent kinase 13 (CDK13)	PF12330 ; PF00069	28.182 (62/220)	3.69E-11
Cyclin-dependent kinase 11A (CDK11A)	PF00069	26.250 (84/320)	3.69E-11
Mitogen-activated protein kinase kinase kinase 15 (MAP3K15)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	25.000 (66/264)	3.78E-11
Aurora kinase C (AURKC)	PF00069	27.103 (58/214)	4.16E-11
Apoptosis signal-regulating kinase 1 (MAP3K5)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	26.415 (70/265)	4.49E-11
Extracellular signal-regulated kinase 2 (ERK2)	PF00069	27.083 (65/240)	4.73E-11
RAC-alpha serine/threonine-protein kinase (AKT1)	PF00169 ; PF00069 ; PF00433 More >>	27.358 (58/212)	4.90E-11
Myosin-IIIb (MYO3B)	PF00612 ; PF00063 ; PF00069 More >>	24.815 (67/270)	5.06E-11
Cyclin-dependent kinase 4 (CDK4)	PF00069	29.493 (64/217)	5.39E-11
MAPK/MAK/MRK overlapping kinase (MOK)	PF00069	25.714 (54/210)	6.22E-11
Mitogen-activated protein kinase 13 (MAPK13)	PF00069	27.941 (57/204)	6.49E-11
IL-1 receptor-associated kinase 3 (IRAK3)	PF00531 ; PF00069	23.279 (71/305)	6.55E-11
Protein kinase C zeta (PRKCZ)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	24.373 (68/279)	6.62E-11
Misshapen-like kinase 1 (MINK1)	PF00780 ; PF00069	24.783 (57/230)	7.09E-11
G protein-coupled receptor kinase 4 (GRK4)	PF00069 ; PF00615	27.941 (57/204)	7.13E-11
Serine/threonine-protein kinase pim-2 (PIM2)	PF00069	24.427 (64/262)	7.30E-11
MAPK/ERK kinase kinase 1 (MAP3K1)	PF00069	25.000 (66/264)	7.37E-11
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	PF00069	27.848 (66/237)	7.58E-11
Serine/threonine-protein kinase Nek8 (NEK8)	PF00069 ; PF00415	26.000 (52/200)	8.03E-11
Yet another novel kinase 2 (STK32B)	PF00069	30.415 (66/217)	8.51E-11
Cyclin-dependent kinase 18 (CDK18)	PF00069	26.087 (54/207)	8.55E-11
ERK activator kinase 5 (MAP2K5)	PF00564 ; PF00069	22.963 (62/270)	8.70E-11
ERK activator kinase 2 (MEK2)	PF00069	25.521 (49/192)	9.20E-11
5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)	PF16579 ; PF00069	29.245 (62/212)	9.71E-11
TAO kinase 1 (TAOK1)	PF00069	26.882 (75/279)	9.90E-11
Cyclin-dependent kinase 15 (CDK15)	PF00069	25.352 (54/213)	1.02E-10
Serine/threonine-protein kinase Sgk2 (SGK2)	PF00069 ; PF00433	26.582 (63/237)	1.17E-10
ERK activator kinase 1 (MEK1)	PF00069	24.771 (54/218)	1.21E-10
Polo-like kinase 2 (PLK2)	PF00069 ; PF00659	23.047 (59/256)	1.28E-10
BR serine/threonine kinase 2 (BRSK2)	PF00069	27.347 (67/245)	1.46E-10
Extracellular signal-regulated kinase 1 (ERK1)	PF00069	27.083 (65/240)	1.69E-10
Protein kinase N3 (PKN3)	PF02185 ; PF00069 ; PF00433 More >>	29.148 (65/223)	1.72E-10
TAO kinase 3 (TAOK3)	PF00069	26.241 (74/282)	1.73E-10
STE20-related serine/threonine-protein kinase (SLK)	PF00069 ; PF12474	24.436 (65/266)	1.84E-10
Serine/threonine-protein kinase WNK4 (WNK4)	PF12202 ; PF00069	26.016 (64/246)	1.89E-10
Serine/threonine-protein kinase Sgk3 (SGK3)	PF00069 ; PF00433 ; PF00787 More >>	27.193 (62/228)	2.00E-10
G protein-coupled receptor kinase 5 (GRK5)	PF00069 ; PF00615	26.961 (55/204)	2.21E-10
Testis-specific serine/threonine-protein kinase 1 (TSSK1B)	PF00069	27.059 (69/255)	2.43E-10
Extracellular signal-regulated kinase 5 (ERK5)	PF00069	27.014 (57/211)	2.51E-10
Serine/threonine-protein kinase NLK (NLK)	PF00069	28.713 (58/202)	2.94E-10
MEK kinase kinase 4 (MAP4K4)	PF00780 ; PF00069	24.664 (55/223)	3.08E-10
Serine/threonine-protein kinase TAO2 (TAOK2)	PF00069	27.542 (65/236)	3.40E-10
Rhodopsin kinase GRK1 (GRK1)	PF00069 ; PF00615	26.961 (55/204)	3.44E-10
Cyclin-dependent kinase 11B (CDK11B)	PF00069	25.938 (83/320)	3.83E-10
NIMA-related kinase 1 (NEK1)	PF00069	25.253 (50/198)	4.12E-10
Stress-activated protein kinase 2b (p38 beta)	PF00069	25.101 (62/247)	4.28E-10
cAMP-dependent protein kinase catalytic subunit gamma (PRKACG)	PF00069	25.000 (56/224)	4.65E-10
Cyclin-dependent kinase 12 (CDK12)	PF00069	27.315 (59/216)	4.83E-10
G protein-coupled receptor kinase 6 (GRK6)	PF00069 ; PF00615	25.743 (52/202)	5.07E-10
Putative 3-phosphoinositide-dependent protein kinase 2 (PDPK2P)	PF00069	24.074 (52/216)	5.78E-10
Serine/threonine-protein kinase ICK (CILK1)	PF00069	25.806 (56/217)	5.87E-10
Putative serine/threonine-protein kinase SIK1B (SIK1B)	PF00069	23.318 (52/223)	6.22E-10
Salt-inducible kinase 1 (SIK1)	PF00069	23.318 (52/223)	6.33E-10
Calmodulin-dependent kinase II (CAMKK2)	PF00069	30.909 (51/165)	6.56E-10
Protein kinase C iota (PRKCI)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	25.991 (59/227)	6.57E-10
SIK family kinase 3 (SIK3)	PF00069	25.214 (59/234)	6.75E-10
WNK lysine-deficient protein kinase 3 (WNK3)	PF12202 ; PF00069	25.792 (57/221)	7.63E-10
Phosphoinositide dependent protein kinase-1 (PDPK1)	PF14593 ; PF00069	24.074 (52/216)	8.75E-10
ERK activator kinase 7 (MAP2K7)	PF00069	22.059 (60/272)	8.76E-10
Mitogen-activated protein kinase 6 (MAPK6)	PF00069	29.108 (62/213)	1.04E-09
Protein kinase N2 (PKN2)	PF02185 ; PF00069 ; PF00433 More >>	29.808 (62/208)	1.27E-09
Cyclin-dependent kinase 10 (CDK10)	PF00069	28.959 (64/221)	1.53E-09
PAK-4 protein kinase (PAK4)	PF00786 ; PF00069	25.991 (59/227)	1.90E-09
Polo-like kinase 1 (PLK1)	PF00069 ; PF00659	35.714 (35/98)	2.00E-09
Doublecortin-like kinase 3 (DCLK3)	PF00069	26.214 (54/206)	2.45E-09
Cyclin-dependent kinase 9 (CDK9)	PF00069	26.316 (55/209)	2.46E-09
Checkpoint kinase-1 (CHK1)	PF00069	30.918 (64/207)	2.48E-09
MEK kinase kinase 3 (MAP4K3)	PF00780 ; PF00069	27.586 (56/203)	2.75E-09
Serine/threonine-protein kinase PAK 6 (PAK6)	PF00786 ; PF00069	27.273 (45/165)	3.02E-09
Protein kinase N1 (PKN1)	PF02185 ; PF00069 ; PF00433 More >>	30.806 (65/211)	3.32E-09
Doublecortin-like kinase 2 (DCLK2)	PF03607 ; PF00069	25.551 (58/227)	3.93E-09
Activin receptor type IIA (ACVR2A)	PF01064 ; PF00069	25.114 (55/219)	3.97E-09
BR serine/threonine kinase 1 (BRSK1)	PF00069	25.926 (63/243)	4.03E-09
Serine/threonine-protein kinase 32C (STK32C)	PF00069	24.183 (74/306)	4.25E-09
cAMP-dependent protein kinase catalytic subunit alpha (PRKACA)	PF00069	23.671 (49/207)	4.29E-09
Serine/threonine-protein kinase PLK3 (PLK3)	PF00069 ; PF00659	25.346 (55/217)	4.75E-09
Calcium/calmodulin-dependent protein kinase type 1D (CAMK1D)	PF00069	26.160 (62/237)	4.79E-09
Death-associated protein kinase 3 (DAPK3)	PF00069	26.875 (43/160)	4.91E-09
Protein kinase C eta type (PRKCH)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	25.854 (53/205)	5.44E-09
Serine/threonine-protein kinase 10 (STK10)	PF00069 ; PF12474	22.761 (61/268)	5.48E-09
Rho-associated protein kinase 2 (ROCK2)	PF00069 ; PF08912	29.048 (61/210)	6.04E-09
Myosin light chain kinase 2 (MYLK2)	PF00069	24.771 (54/218)	8.57E-09
Tyrosine-protein kinase EIF2AK2 (p68)	PF00035 ; PF00069	31.868 (29/91)	8.98E-09
MAP kinase p38 (MAPK12)	PF00069	27.184 (56/206)	9.69E-09
Death-associated protein kinase 1 (DAPK1)	PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF00069 More >>	27.500 (44/160)	1.00E-08
cAMP-dependent protein kinase catalytic subunit beta (PRKACB)	PF00069	23.077 (48/208)	1.07E-08
Cyclin-dependent kinase 19 (CDK19)	PF00069	26.415 (56/212)	1.12E-08
Cyclin-dependent kinase 14 (CDK14)	PF00069	24.762 (52/210)	1.14E-08
Rhodopsin kinase GRK7 (GRK7)	PF00069 ; PF00615	28.302 (60/212)	1.18E-08
Doublecortin-like kinase 1 (DCLK1)	PF03607 ; PF00069	28.230 (59/209)	1.24E-08
Rho-associated protein kinase 1 (ROCK1)	PF00069 ; PF08912	29.524 (62/210)	1.41E-08
Protein kinase C gamma (PRKCG)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	29.104 (39/134)	1.96E-08
Protein kinase G1 (PRKG1)	PF00027 ; PF16808 ; PF00069 More >>	24.561 (56/228)	2.20E-08
TGF-beta receptor type I (TGFBR1)	PF01064 ; PF00069 ; PF08515 More >>	25.676 (57/222)	2.53E-08
MEK kinase kinase 2 (MAP4K2)	PF00780 ; PF00069	24.490 (48/196)	2.79E-08
Serine/threonine-protein kinase MAK (MAK)	PF00069	27.442 (59/215)	3.15E-08
Testis-specific serine/threonine-protein kinase 4 (TSSK4)	PF00069	28.667 (43/150)	4.11E-08
Serine/threonine-protein kinase WNK1 (WNK1)	PF12202 ; PF00069	24.286 (51/210)	5.41E-08
Death-associated protein kinase 2 (DAPK2)	PF00069	26.415 (56/212)	5.61E-08
Serine/threonine-protein kinase SBK1 (SBK1)	PF00069	26.891 (64/238)	5.62E-08
Cyclin-dependent kinase 20 (CDK20)	PF00069	24.255 (57/235)	5.75E-08
Myosin light kinase (MYLK)	PF16620 ; PF00041 ; PF07679 ; PF00069 More >>	24.390 (50/205)	5.82E-08
TBC domain-containing protein kinase-like protein (TBCK)	PF00069 ; PF00566 ; PF00581 More >>	26.829 (44/164)	6.13E-08
Cyclin-dependent kinase-like 4 (CDKL4)	PF00069	23.853 (52/218)	6.39E-08
Serine/threonine-protein kinase cot (COT)	PF00069	27.536 (57/207)	6.43E-08
SNF-related serine/threonine-protein kinase (SNRK)	PF00069	22.568 (58/257)	8.12E-08
Aurora kinase B (AURKB)	PF00069	26.415 (56/212)	9.94E-08
Nik-related protein kinase (NRK)	PF00780 ; PF00069	22.989 (60/261)	1.05E-07
Cyclin-dependent kinase-like 3 (CDKL3)	PF00069	21.402 (58/271)	1.13E-07
Cyclin-dependent kinase-like 2 (CDKL2)	PF00069	24.775 (55/222)	1.51E-07
Activin receptor type IIB (ACVR2B)	PF01064 ; PF00069	22.830 (71/311)	1.74E-07
Cyclin-dependent kinase-like 1 (CDKL1)	PF00069	25.000 (55/220)	1.75E-07
Apoptosis signal-regulating kinase 2 (MAP3K6)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	25.110 (57/227)	1.96E-07
Ribosomal protein S6 kinase alpha-4 (RPS6KA4)	PF00069 ; PF00433	21.756 (57/262)	1.99E-07
Mitogen-activated protein kinase 4 (MAPK4)	PF00069	27.568 (51/185)	2.08E-07
Phosphorylase kinase testis gamma 2 (PHKG2)	PF00069	22.449 (55/245)	2.21E-07
Activin receptor type IB (ACVR1B)	PF01064 ; PF00069 ; PF08515 More >>	24.324 (54/222)	2.27E-07
Triple functional domain protein (TRIO)	PF00650 ; PF07679 ; PF00169 ; PF00069 ; PF00621 ; PF16609 ; PF00018 ; PF00435 More >>	28.774 (61/212)	2.30E-07
Cyclin-dependent kinase 8 (CDK8)	PF00069	25.837 (54/209)	2.52E-07
Protein kinase G2 (PRKG2)	PF00027 ; PF00069	24.701 (62/251)	2.60E-07
Testis-specific serine/threonine-protein kinase 3 (TSSK3)	PF00069	23.404 (55/235)	2.62E-07
MAPK/ERK kinase kinase 4 (MAP3K4)	PF19431 ; PF00069	20.863 (58/278)	2.72E-07
Kalirin (KALRN)	PF13716 ; PF00041 ; PF07679 ; PF00169 ; PF00069 ; PF00621 ; PF16609 ; PF00435 More >>	24.312 (53/218)	3.40E-07
Beta-adrenergic receptor kinase 1 (ADRBK1)	PF00169 ; PF00069 ; PF00615 More >>	25.701 (55/214)	3.74E-07
Calcium/calmodulin-dependent protein kinase type 1B (PNCK)	PF00069	26.047 (56/215)	4.55E-07
PRKR-like endoplasmic reticulum kinase (PERK)	PF00069	33.010 (34/103)	4.62E-07
Serine/threonine-protein kinase NIM1 (NIM1K)	PF00069	23.457 (57/243)	5.28E-07
Beta-adrenergic receptor kinase 2 (ADRBK2)	PF00169 ; PF00069 ; PF00615 More >>	25.234 (54/214)	5.49E-07
Anti-mullerian hormone II receptor (AMHR2)	PF00069	21.587 (68/315)	6.03E-07
Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)	PF00069 ; PF18394 ; PF18396 More >>	26.027 (57/219)	6.45E-07
Microtubule-associated serine/threonine-protein kinase 3 (MAST3)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	23.636 (52/220)	9.81E-07
Serine/threonine-protein kinase PDIK1L (PDIK1L)	PF00069	23.729 (70/295)	1.02E-06
Stress-activated protein kinase JNK3 (JNK3)	PF00069	25.926 (56/216)	1.10E-06
Testis-specific serine/threonine-protein kinase 6 (TSSK6)	PF00069	27.083 (65/240)	1.32E-06
Striated muscle preferentially expressed protein kinase (SPEG)	PF07679 ; PF00069 ; PF16650 More >>	23.967 (29/121)	1.75E-06
Ribosomal protein S6 kinase-related protein (RSKR)	PF00069	31.000 (31/100)	1.86E-06
Serine/threonine-protein kinase 17B (STK17B)	PF00069	25.564 (34/133)	2.85E-06
Serine/threonine-protein kinase 35 (STK35)	PF00069	24.127 (76/315)	2.97E-06
Bone morphogenetic protein receptor (BMPR2)	PF01064 ; PF00069	21.942 (61/278)	3.13E-06
Calcium/calmodulin-dependent protein kinase type 1G (CAMK1G)	PF00069	26.442 (55/208)	3.29E-06
Ribosomal protein S6 kinase alpha-5 (RSK5)	PF00069 ; PF00433	23.697 (50/211)	3.41E-06
Eukaryotic translation initiation factor 2-alpha kinase 4 (EIF2AK4)	PF12745 ; PF00069 ; PF05773 ; PF13393 More >>	26.471 (36/136)	3.71E-06
Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6)	PF00069	25.248 (51/202)	4.60E-06
Dual-specificity tyrosine-phosphorylation regulated kinase 3 (DYRK3)	PF00069	26.812 (37/138)	5.23E-06
Serine/threonine-protein kinase pim-1 (PIM1)	PF00069	23.894 (54/226)	5.28E-06
Homeodomain-interacting protein kinase 4 (HIPK4)	PF00069	32.258 (40/124)	5.39E-06
Stress-activated protein kinase JNK2 (JNK2)	PF00069	26.733 (54/202)	5.80E-06
Obscurin (OBSCN)	PF00041 ; PF07679 ; PF00612 ; PF00069 ; PF00621 More >>	25.854 (53/205)	5.95E-06
Microtubule-associated serine/threonine-protein kinase 1 (MAST1)	PF08926 ; PF17820 ; PF00069 More >>	22.857 (48/210)	7.17E-06
Calcium/calmodulin-dependent protein kinase type II subunit gamma (CAMK2G)	PF08332 ; PF00069	25.904 (43/166)	7.47E-06
Serine/threonine-protein kinase H2 (PSKH2)	PF00069	22.905 (41/179)	8.19E-06
NF-kappa-B-activating kinase (TBK1)	PF00069 ; PF18394 ; PF18396 More >>	23.502 (51/217)	8.70E-06
Stress-activated protein kinase JNK1 (JNK1)	PF00069	24.752 (50/202)	1.04E-05
PIM-3 protein kinase (PIM3)	PF00069	27.488 (58/211)	1.14E-05
Glycogen synthase kinase-3 beta (GSK-3B)	PF00069	23.549 (69/293)	1.32E-05
CaM-kinase IV kinase (CAMKK1)	PF00069	35.632 (31/87)	1.32E-05
Mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5)	PF00780 ; PF00069	24.000 (48/200)	1.44E-05
Microtubule-associated serine/threonine-protein kinase 2 (MAST2)	PF08926 ; PF17820 ; PF00069 More >>	22.857 (48/210)	1.52E-05
Interleukin-1 receptor-associated kinase-like 2 (IRAK2)	PF00531 ; PF00069	23.039 (47/204)	1.58E-05
Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1)	PF00069	31.683 (32/101)	1.81E-05
Glycogen synthase kinase-3 alpha (GSK-3A)	PF00069	23.377 (54/231)	1.96E-05
Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3)	PF00069	23.348 (53/227)	2.26E-05
PAS domain-containing serine/threonine-protein kinase (PASK)	PF13426 ; PF00069	24.020 (49/204)	2.72E-05
Microtubule-associated serine/threonine-protein kinase 4 (MAST4)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	22.857 (48/210)	2.99E-05
Homeodomain-interacting protein kinase 1 (HIPK1)	PF00069	25.806 (64/248)	3.11E-05
Homeodomain-interacting protein kinase 3 (HIPK3)	PF00069	25.490 (65/255)	3.28E-05
Serine/threonine-protein kinase H1 (PSKH1)	PF00069	24.324 (54/222)	3.62E-05
Serine/threonine-protein kinase tousled-like 2 (TLK2)	PF00069	27.976 (47/168)	3.79E-05
Serine/threonine-protein kinase MRCK beta (CDC42BPB)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 More >>	24.413 (52/213)	3.88E-05
Serine/threonine-protein kinase STK11 (STK11)	PF00069	22.917 (44/192)	3.91E-05
Casein kinase II alpha (CSNK2A1)	PF00069	22.330 (46/206)	3.93E-05
Cytoplasmic DRAK1 (STK17A)	PF00069	25.926 (35/135)	4.41E-05
Homeodomain interacting protein kinase 2 (HIPK2)	PF00069	26.641 (69/259)	5.43E-05
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A)	PF08332 ; PF00069	25.301 (42/166)	5.64E-05
Cyclin-dependent kinase-like 5 (CDKL5)	PF00069	23.832 (51/214)	6.04E-05
Serine/threonine-protein kinase ULK4 (ULK4)	PF00069	24.725 (45/182)	6.84E-05
Calcium/calmodulin-dependent protein kinase type IV (CAMK4)	PF00069	26.432 (60/227)	7.37E-05
MAPK-activated protein kinase 2 (MAPKAPK2)	PF00069	25.610 (42/164)	1.06E-04
Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)	PF08332 ; PF00069	25.904 (43/166)	1.21E-04
MEK kinase kinase 1 (MAP4K1)	PF00780 ; PF00069	24.457 (45/184)	1.30E-04
Casein kinase II alpha prime (CSNK2A2)	PF00069	22.603 (33/146)	1.67E-04
Calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B)	PF08332 ; PF00069	28.571 (30/105)	1.70E-04
CDC42 binding protein kinase alpha (DMPK-like alpha)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 ; PF00433 More >>	23.944 (51/213)	1.73E-04
Citron Rho-interacting kinase (CIT)	PF00780 ; PF00169 ; PF00069 More >>	25.000 (57/228)	1.79E-04
CaM kinase-like vesicle-associated protein (CAMKV)	PF00069	24.064 (45/187)	2.19E-04
Casein kinase II subunit alpha 3 (CSNK2A3)	PF00069	21.605 (35/162)	3.51E-04
MAPK-activated protein kinase 3 (MAPKAPK3)	PF00069	25.926 (35/135)	5.46E-04
Serine/threonine-protein kinase Chk2 (RAD53)	PF00498 ; PF00069	24.852 (42/169)	5.63E-04
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (PHKG1)	PF00069	23.952 (40/167)	6.01E-04
Serine/threonine-protein kinase NIK (MAP3K14)	PF00069	23.762 (48/202)	6.79E-04
BMP-2-inducible protein kinase (BMP2K)	PF15282 ; PF00069	24.537 (53/216)	7.93E-04
Serine/threonine kinase-like domain-containing protein STKLD1 (STKLD1)	PF00069	28.723 (27/94)	1.00E-03
Serine/threonine-protein kinase greatwall (MASTL)	PF00069	25.000 (42/168)	1.00E-03
Serine/threonine-protein kinase/endoribonuclease IRE2 (ERN2)	PF00069 ; PF06479	28.413 (77/271)	1.00E-03
Serine/threonine-protein kinase tousled-like 1 (TLK1)	PF00069	25.749 (43/167)	1.00E-03
NDR2 protein kinase (STK38L)	PF00069 ; PF00433	21.097 (50/237)	2.00E-03
Peripheral plasma membrane protein CASK (CASK)	PF00625 ; PF02828 ; PF00595 ; PF00069 ; PF00018 More >>	22.170 (47/212)	2.00E-03
Adaptor-associated kinase 1 (AAK1)	PF00069	22.018 (48/218)	3.00E-03
Endoplasmic reticulum to nucleus signaling 1 (ERN1)	PF00069 ; PF06479	21.719 (48/221)	4.00E-03
Cyclin-G-associated kinase (GAK)	PF00069 ; PF10409	22.594 (54/239)	4.00E-03
Serine/threonine-protein kinase SBK2 (SBK2)	PF00069	24.615 (48/195)	5.00E-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
Axon guidance	hsa04360	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy
Focal adhesion	hsa04510	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Adherens junction	hsa04520	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	35	Degree centrality	3.76E-03	Betweenness centrality	2.68E-03
Closeness centrality	2.51E-01	Radiality	1.44E+01	Clustering coefficient	2.22E-01
Neighborhood connectivity	5.52E+01	Topological coefficient	6.69E-02	Eccentricity	12
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		Top
KEGG Pathway	[+] 18 KEGG Pathways	+
1	Ras signaling pathway
2	Rap1 signaling pathway
3	Cytokine-cytokine receptor interaction
4	Endocytosis
5	PI3K-Akt signaling pathway
6	Axon guidance
7	Focal adhesion
8	Adherens junction
9	Bacterial invasion of epithelial cells
10	Epithelial cell signaling in Helicobacter pylori infection
11	Malaria
12	Pathways in cancer
13	Transcriptional misregulation in cancer
14	Proteoglycans in cancer
15	MicroRNAs in cancer
16	Renal cell carcinoma
17	Melanoma
18	Central carbon metabolism in cancer
PID Pathway	[+] 10 PID Pathways	+
1	Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
2	Arf6 signaling events
3	Signaling events mediated by TCPTP
4	Posttranslational regulation of adherens junction stability and dissassembly
5	Direct p53 effectors
6	Syndecan-1-mediated signaling events
7	Stabilization and expansion of the E-cadherin adherens junction
8	a6b1 and a6b4 Integrin signaling
9	FGF signaling pathway
10	Regulation of retinoblastoma protein
Reactome	[+] 1 Reactome Pathways	+
1	Sema4D mediated inhibition of cell attachment and migration
WikiPathways	[+] 10 WikiPathways	+
1	TGF beta Signaling Pathway
2	Signaling of Hepatocyte Growth Factor Receptor
3	Focal Adhesion
4	Extracellular vesicle-mediated signaling in recipient cells
5	Signaling Pathways in Glioblastoma
6	miR-targeted genes in squamous cell - TarBase
7	miR-targeted genes in muscle cell - TarBase
8	miR-targeted genes in lymphocytes - TarBase
9	miR-targeted genes in epithelium - TarBase
10	Semaphorin interactions

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 2

FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 761210.

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ClinicalTrials.gov (NCT02478866) Safety and Pharmacokinetics of BPI-9016M in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 36

ClinicalTrials.gov (NCT03672305) Clinical Study on the Efficacy and Safety of c-Met/PD-L1 CAR-T Cell Injection in the Treatment of HCC

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REF 38

ClinicalTrials.gov (NCT02533102) Pharmacokinetics and Food Effect of Single Oral Dose of E7050 in Healthy Volunteers.

REF 39

ClinicalTrials.gov (NCT01110083) First-in-Man, Dose-escalation Trial of c-Met Kinase Inhibitor EMD 1204831 in Subjects With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 40

Pharmacokinetics and biochemical effects of hepapoietin in patients with chronic liver disease. Aliment Pharmacol Ther. 2002 Feb;16(2):235-42.

REF 41

ClinicalTrials.gov (NCT00651365) A Safety and Dose-finding Study of JNJ-38877605 in Patients With Advanced or Refractory Solid Tumors.. U.S. National Institutes of Health.

REF 42

ClinicalTrials.gov (NCT02221882) A Study of LY3164530 in Participants With Cancer

REF 43

ClinicalTrials.gov (NCT00559182) A Study of MK-8033 in Patients With Advanced Solid Tumors (MK-8033-001). U.S. National Institutes of Health.

REF 44

ClinicalTrials.gov (NCT00706355) A Study of PF-04217903 in Patients With Advanced Cancer. U.S. National Institutes of Health.

REF 45

ClinicalTrials.gov (NCT04077099) REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung Cancer. U.S. National Institutes of Health.

REF 46

ClinicalTrials.gov (NCT03454243) Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors (TITAN). U.S. National Institutes of Health.

REF 47

REF 48

ClinicalTrials.gov (NCT00607399) Safety Study of SGX523, a Small Molecule Met Inhibitor, to Treat Solid Tumors. U.S. National Institutes of Health.

REF 49

ClinicalTrials.gov (NCT03993873) Phase 1 Study of TPX-0022, a MET/CSF1R/SRC Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in MET. U.S. National Institutes of Health.

REF 50

ClinicalTrials.gov (NCT03859752) TR1801-ADC in Patients With Tumors That Express c-Met. U.S. National Institutes of Health.

REF 51

ClinicalTrials.gov (NCT03845166) A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors. U.S. National Institutes of Health.

REF 52

Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22.

REF 53

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications. Mol Cancer. 2019 Nov 4;18(1):153.

REF 54

Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.

REF 55

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Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.

REF 57

REF 58

Role and relevance of TrkB mutations and expression in non-small cell lung cancer. Clin Cancer Res. 2011 May 1;17(9):2638-45.

REF 59

A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors. Oncotarget. 2015 Jul 30;6(21):18693-706.

REF 60

J Clin Oncol 32:5s, 2014 (suppl; abstr 2508).

REF 61

Clinical pipeline report, company report or official report of Apollomics.

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

REF 63

Clinical pipeline report, company report or official report of Eli Lilly.

REF 64

LY2875358, a neutralizing and internalizing anti-MET bivalent antibody, inhibits HGF-dependent and HGF-independent MET activation and tumor growth. Clin Cancer Res. 2014 Dec 1;20(23):6059-70.

REF 65

Clinical pipeline report, company report or official report of Eli Lilly.

REF 66

LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2013 Aug;31(4):833-44.

REF 67

The selective intravenous inhibitor of the MET tyrosine kinase SAR125844 inhibits tumor growth in MET-amplified cancer. Mol Cancer Ther. 2015 Feb;14(2):384-94.

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Clinical pipeline report, company report or official report of AbbVie.

REF 69

Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

REF 70

Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607... J Med Chem. 2009 Mar 12;52(5):1251-4.

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J Clin Oncol 32:5s, 2014 (suppl; abstr 2507).

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Clinical pipeline report, company report or official report of Deciphera Pharmaceuticals.

REF 74

Clinical pipeline report, company report or official report of AstraZeneca

REF 75

First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer. J Hematol Oncol. 2020 Jan 16;13(1):6.

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E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5.

REF 77

2012 ASCO Annual Meeting.

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Pharmacokinetics and biochemical effects of hepapoietin in patients with chronic liver disease. Alimentary Pharmacology & Therapeutics Volume 16, Issue 2, pages 235-242, February 2002.

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A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.

REF 82

Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther. 2012 Apr;11(4):1036-47.

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NPS-1034, a novel MET inhibitor, inhibits the activated MET receptor and its constitutively active mutants. Invest New Drugs. 2014 Jun;32(3):389-99.

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c-Met inhibitors with novel binding mode show activity against several hereditary papillary renal cell carcinoma-related mutations. J Biol Chem. 2008 Feb 1;283(5):2675-83.

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Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met. Nat Med. 2015 Aug;21(8):955-61.

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Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by incorporation of a 3-amidobenzazepin-2-one group. Bioorg Med Chem. 2011 Nov 1;19(21):6274-84.

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Design and synthesis of novel 3-(benzo[d]oxazol-2-yl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine derivatives as selective G-protein-coupled receptor kinase-2 and -5 inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6711-6.

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