Target Information

Target General Information

Target ID

T59102 (Former ID: TTDR01217)

Target Name

Platelet-derived growth factor receptor beta (PDGFRB)

Synonyms

Platelet-derived growth factor receptor 1; PDGFR1; PDGFR-beta; PDGFR-1; PDGFR; PDGF-R-beta; CD140b antigen; CD140b; CD140 antigen-like family member B; Beta-type platelet-derived growth factor receptor; Beta-PDGFR; Beta platelet-derived growth factor receptor

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Gene Name

PDGFRB

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

Acute diabete complication [ICD-11: 5A2Y]

Renal cell carcinoma [ICD-11: 2C90]

Thrombocytopenia [ICD-11: 3B64]

Function

Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration.

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BioChemical Class

Kinase

UniProt ID

PGFRB_HUMAN

EC Number

EC 2.7.10.1

Sequence

MRLPGAMPALALKGELLLLSLLLLLEPQISQGLVVTPPGPELVLNVSSTFVLTCSGSAPV
VWERMSQEPPQEMAKAQDGTFSSVLTLTNLTGLDTGEYFCTHNDSRGLETDERKRLYIFV
PDPTVGFLPNDAEELFIFLTEITEITIPCRVTDPQLVVTLHEKKGDVALPVPYDHQRGFS
GIFEDRSYICKTTIGDREVDSDAYYVYRLQVSSINVSVNAVQTVVRQGENITLMCIVIGN
EVVNFEWTYPRKESGRLVEPVTDFLLDMPYHIRSILHIPSAELEDSGTYTCNVTESVNDH
QDEKAINITVVESGYVRLLGEVGTLQFAELHRSRTLQVVFEAYPPPTVLWFKDNRTLGDS
SAGEIALSTRNVSETRYVSELTLVRVKVAEAGHYTMRAFHEDAEVQLSFQLQINVPVRVL
ELSESHPDSGEQTVRCRGRGMPQPNIIWSACRDLKRCPRELPPTLLGNSSEEESQLETNV
TYWEEEQEFEVVSTLRLQHVDRPLSVRCTLRNAVGQDTQEVIVVPHSLPFKVVVISAILA
LVVLTIISLIILIMLWQKKPRYEIRWKVIESVSSDGHEYIYVDPMQLPYDSTWELPRDQL
VLGRTLGSGAFGQVVEATAHGLSHSQATMKVAVKMLKSTARSSEKQALMSELKIMSHLGP
HLNVVNLLGACTKGGPIYIITEYCRYGDLVDYLHRNKHTFLQHHSDKRRPPSAELYSNAL
PVGLPLPSHVSLTGESDGGYMDMSKDESVDYVPMLDMKGDVKYADIESSNYMAPYDNYVP
SAPERTCRATLINESPVLSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLV
KICDFGLARDIMRDSNYISKGSTFLPLKWMAPESIFNSLYTTLSDVWSFGILLWEIFTLG
GTPYPELPMNEQFYNAIKRGYRMAQPAHASDEIYEIMQKCWEEKFEIRPPFSQLVLLLER
LLGEGYKKKYQQVDEEFLRSDHPAILRSQARLPGFHGLRSPLDTSSVLYTAVQPNEGDND
YIIPLPDPKPEVADEGPLEGSPSLASSTLNEVNTSSTISCDSPLEPQDEPEPEPQLELQV
EPEPELEQLPDSGCPAPRAEAEDSFL

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

HIT2.0 ID

T34VFO

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 2 Approved Drugs

Becaplermin

Drug Info

Approved

Diabetic complication

[4]

Romiplostim

Drug Info

Approved

Thrombocytopenia

[5], [6]

Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

E-3810

Drug Info

Phase 3

Solid tumour/cancer

[7], [8]

XL-820

Drug Info

Phase 2

Solid tumour/cancer

[11]

MK-2461

Drug Info

Phase 1/2

Alzheimer disease

[12]

SNN-0031

Drug Info

Phase 1/2

Brain injury

[13]

TAK-593

Drug Info

Phase 1

Solid tumour/cancer

[14]

Discontinued Drug(s)

[+] 3 Discontinued Drugs

CDP-860

Drug Info

Discontinued in Phase 2

Solid tumour/cancer

[15]

SRI-62-834

Drug Info

Discontinued in Phase 2

Solid tumour/cancer

[16]

CEP-2563

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[17]

Mode of Action

[+] 2 Modes of Action

Modulator

[+] 4 Modulator drugs

Becaplermin

Drug Info

[18]

SNN-0031

Drug Info

[21]

TAK-593

Drug Info

[14], [22]

CDP-860

Drug Info

[25]

Inhibitor

[+] 99 Inhibitor drugs

Romiplostim

Drug Info

[1]

E-3810

Drug Info

[19]

XL-820

Drug Info

[20]

MK-2461

Drug Info

[12]

PMID25656651-Compound-21a

Drug Info

[23]

Pyridine derivative 18

Drug Info

[24]

SRI-62-834

Drug Info

[26]

CEP-2563

Drug Info

[26]

AG1295

Drug Info

[27]

RG-13022

Drug Info

[28]

(1H-indol-2-yl)(5-methoxy-1H-indol-2-yl)methanone

Drug Info

[29]

(1H-indol-2-yl)(5-phenoxy-1H-indol-2-yl)methanone

Drug Info

[29]

(1H-indol-2-yl)(6-methoxy-1H-indol-2-yl)methanone

Drug Info

[29]

(2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamine

Drug Info

[30]

(5-fluoro-1H-indol-2-yl)-(1H-indol-2-yl)methanone

Drug Info

[29]

(benzo[b]furan-2-yl)-(1H-indol-2-yl)methanone

Drug Info

[27]

1-Phenyl-1H-benzoimidazol-5-ol

Drug Info

[31]

1-Phenyl-1H-benzoimidazole

Drug Info

[31]

3-((E)-Styryl)-quinoline

Drug Info

[28]

3-(1H-Indol-3-yl)-6,7-dimethoxy-quinoline

Drug Info

[28]

3-(1H-Indol-3-yl)-quinoline

Drug Info

[28]

3-(2-Cyclohexyl-ethyl)-6,7-dimethoxy-quinoline

Drug Info

[28]

3-(3,4-Dichloro-phenyl)-6,7-dimethoxy-quinoline

Drug Info

[28]

3-(3,4-Difluoro-phenyl)-6,7-dimethoxy-quinoline

Drug Info

[28]

3-(3,4-Dimethoxy-phenyl)-6,7-dimethoxy-quinoline

Drug Info

[28]

3-(3-Fluoro-phenyl)-6,7-dimethoxy-quinoline

Drug Info

[28]

3-(4-dimethylamino-benzylidenyl)-2-indolinone

Drug Info

[32]

3-(4-Fluoro-phenyl)-6,7-dimethoxy-quinoline

Drug Info

[28]

3-(6,7-Dimethoxy-quinolin-4-yloxy)-phenol

Drug Info

[33]

3-(6,7-Dimethoxy-quinolin-4-yloxy)-phenylamine

Drug Info

[33]

3-Benzimidazol-2-ylhydroquinolin-2-one

Drug Info

[34]

3-Benzyloxy-6,7-dimethoxy-quinoline

Drug Info

[28]

3-Cyclohexylethynyl-6,7-dimethoxy-quinoline

Drug Info

[28]

3-Cyclopent-1-enyl-6,7-dimethoxy-quinoline

Drug Info

[28]

3-Cyclopentyl-6,7-dimethoxy-quinoline

Drug Info

[28]

3-Pyridin-3-yl-quinoline-6,7-diol

Drug Info

[28]

3-Pyridin-4-yl-quinolin-7-ol

Drug Info

[35]

3-Pyridin-4-yl-quinoline

Drug Info

[35]

3-Pyridin-4-yl-quinoline-5,7-diol

Drug Info

[35]

3-Thiophen-3-yl-quinoline

Drug Info

[28]

4-(2,3-Dimethoxy-phenoxy)-6,7-dimethoxy-quinoline

Drug Info

[33]

4-(3,5-Dimethoxy-phenoxy)-6,7-dimethoxy-quinoline

Drug Info

[33]

4-(3-Bromo-phenoxy)-6,7-dimethoxy-quinazoline

Drug Info

[33]

4-(3-Bromo-phenoxy)-6,7-dimethoxy-quinoline

Drug Info

[33]

4-(3-Ethyl-phenoxy)-6,7-dimethoxy-quinoline

Drug Info

[33]

4-(3-Fluoro-phenoxy)-6,7-dimethoxy-quinoline

Drug Info

[33]

4-(5-Methoxy-benzoimidazol-1-yl)-phenylamine

Drug Info

[36]

4-(6,7-Dimethoxy-quinolin-3-yl)-benzoic acid

Drug Info

[28]

4-(6,7-Dimethoxy-quinolin-3-yl)-phenol

Drug Info

[28]

4-Benzoimidazol-1-yl-phenylamine

Drug Info

[31]

5,6,7-Trimethoxy-3-pyridin-4-yl-quinoline

Drug Info

[35]

5,7-Dimethoxy-3-pyridin-4-yl-quinoline

Drug Info

[35]

5,7-Dimethoxy-3-thiophen-3-yl-quinoline

Drug Info

[28]

5,7-Dimethyl-3-thiophen-3-yl-quinoline

Drug Info

[28]

5-(6,7-Dimethoxy-quinolin-3-yl)-1H-pyridin-2-one

Drug Info

[28]

5-Methoxy-1-phenyl-1H-benzoimidazole

Drug Info

[31]

6,7-Dichloro-3-thiophen-3-yl-quinoline

Drug Info

[28]

6,7-Difluoro-3-thiophen-3-yl-quinoline

Drug Info

[28]

6,7-Dimethoxy-3-((E)-styryl)-quinoline

Drug Info

[28]

6,7-Dimethoxy-3-(3-methoxy-phenyl)-quinoline

Drug Info

[28]

6,7-Dimethoxy-3-(4-methoxy-phenyl)-quinoline

Drug Info

[28]

6,7-Dimethoxy-3-(4-nitro-phenyl)-quinoline

Drug Info

[28]

6,7-Dimethoxy-3-p-tolyl-quinoline

Drug Info

[28]

6,7-Dimethoxy-3-phenyl-quinoline

Drug Info

[28]

6,7-Dimethoxy-3-pyridin-3-yl-quinoline

Drug Info

[28]

6,7-Dimethoxy-3-pyridin-4-yl-quinoline

Drug Info

[35]

6,7-Dimethoxy-3-thiophen-2-yl-quinoline

Drug Info

[28]

6,7-Dimethoxy-4-(2-methoxy-phenoxy)-quinoline

Drug Info

[33]

6,7-Dimethoxy-4-(3-methoxy-phenoxy)-quinoline

Drug Info

[33]

6,7-Dimethoxy-4-(4-methoxy-phenoxy)-quinoline

Drug Info

[33]

6,7-Dimethoxy-4-phenoxy-quinoline

Drug Info

[33]

6-Methoxy-3-pyridin-4-yl-quinoline

Drug Info

[35]

7-Fluoro-3-thiophen-3-yl-quinoline

Drug Info

[28]

7-Methoxy-3-pyridin-4-yl-quinoline

Drug Info

[35]

7-Thiophen-3-yl-[1,3]dioxolo[4,5-g]quinoline

Drug Info

[28]

Benzyl-(6,7-dimethoxy-quinolin-3-yl)-amine

Drug Info

[28]

Bis(5-acetoxybenzo[b]furan-2-yl)methanone

Drug Info

[27]

Bis(5-aminobenzo[b]furan-2-yl)methanone

Drug Info

[27]

Bis(5-hydroxybenzo[b]furan-2-yl)methanone

Drug Info

[27]

Bis(5-methoxybenzo[b]furan-2-yl)methanone

Drug Info

[27]

Bis(6-hydroxybenzo[b]furan-2-yl)methanone

Drug Info

[27]

Bis-(5-hydroxy-1H-indol-2-yl)-methanone

Drug Info

[29]

BMS-536924

Drug Info

[37]

CP-673451

Drug Info

[38]

Di(1H-indol-2-yl)methanone

Drug Info

[29]

HKI-9924129

Drug Info

[39]

Ki-11502

Drug Info

[40]

Ki-20227

Drug Info

[41]

PD-0166326

Drug Info

[39]

PD-0173952

Drug Info

[39]

PD-0173955

Drug Info

[39]

PD-0173956

Drug Info

[39]

PD-0179483

Drug Info

[39]

PDGF receptor tyrosine kinase inhibitor III

Drug Info

[42]

PMID22765894C8h

Drug Info

[43]

Ro-4396686

Drug Info

[44]

RPR-108514A

Drug Info

[45]

SU-11652

Drug Info

[1]

TG-100435

Drug Info

[46]

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: 2-(Acetylamino)-2-Deoxy-a-D-Glucopyranose

Ligand Info

Structure Description

The structure of a platelet derived growth factor receptor complex

PDB:3MJG

Method

X-ray diffraction

Resolution

2.30 Å

Mutation

[48]

PDB Sequence

LVVTPPGPEL

⁴²

VLNVSSTFVL

⁵²

TCSGSAPVVW

⁶²

ERMSQEPPQE

⁷²

MAKAQDGTFS

⁸²

SVLTLTNLTG

⁹²

LDTGEYFCTH

¹⁰²

NDDERKRLYI

¹¹⁸

FVPDPTVGFL

¹²⁸

PNDAEELFIF

¹³⁸

LTEITEITIP

¹⁴⁸

CRVTDPQLVV

¹⁵⁸

TLHEKKGDVA

¹⁶⁸

LPVPYDHQRG

¹⁷⁸

FSGIFEDRSY

¹⁸⁸

ICKTTIGDRE

¹⁹⁸

VDSDAYYVYR

²⁰⁸

LQVSSINVSV

²¹⁸

NAVQTVVRQG

²²⁸

ENITLMCIVI

²³⁸

GNEVVNFEWT

²⁴⁸

YPRKESGRLV

²⁵⁸

EPVTDFLLDM

²⁶⁸

PYHIRSILHI

²⁷⁸

PSAELEDSGT

²⁸⁸

YTCNVTESVN

²⁹⁸

DHQDEKAINI

³⁰⁸

TVVE

Residue

Distance (Å)

ASN45

1.451

Residue

Distance (Å)

SER48

4.640

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	32.000 (56/175)	5.21E-20
SPS1/STE20-related protein kinase YSK4 (YSK4)	PF00069	29.609 (53/179)	4.87E-13
Extracellular signal-regulated kinase 1 (ERK1)	PF00069	36.449 (39/107)	2.74E-12
Cyclin-dependent kinase 6 (CDK6)	PF00069	30.822 (45/146)	2.77E-12
Serine/threonine-protein kinase 24 (STK24)	PF00069	32.667 (49/150)	4.05E-12
Extracellular signal-regulated kinase 2 (ERK2)	PF00069	36.893 (38/103)	4.08E-12
Serine/threonine-protein kinase Nek4 (NEK4)	PF00069	29.730 (44/148)	1.41E-11
Cyclin-dependent kinase-like 2 (CDKL2)	PF00069	30.328 (37/122)	1.95E-11
Serine/threonine-protein kinase ICK (CILK1)	PF00069	36.842 (42/114)	2.20E-11
Cyclin-dependent kinase 4 (CDK4)	PF00069	38.202 (34/89)	3.34E-11
STE20-related serine/threonine-protein kinase (SLK)	PF00069 ; PF12474	31.210 (49/157)	7.45E-11
ERK activator kinase 5 (MAP2K5)	PF00564 ; PF00069	37.864 (39/103)	8.29E-11
Serine/threonine-protein kinase 25 (STK25)	PF00069	32.000 (48/150)	1.03E-10
PKC-delta-interacting protein kinase (RIPK4)	PF12796 ; PF00069	29.487 (46/156)	1.27E-10
Serine/threonine-protein kinase 26 (STK26)	PF00069	38.889 (35/90)	1.27E-10
Tyrosine-protein kinase EIF2AK2 (p68)	PF00035 ; PF00069	27.815 (42/151)	1.30E-10
Serine/threonine-protein kinase 3 (STK3)	PF11629 ; PF00069	31.973 (47/147)	1.34E-10
PAK-1 protein kinase (PAK1)	PF00786 ; PF00069	30.345 (44/145)	1.36E-10
Oxidative stress responsive 1 (OXSR1)	PF12202 ; PF00069	34.959 (43/123)	2.58E-10
PAK-2 protein kinase (PAK2)	PF00786 ; PF00069	31.159 (43/138)	3.60E-10
NIMA-related kinase 7 (NEK7)	PF00069	28.662 (45/157)	3.71E-10
MST-1 protein kinase (STK4)	PF11629 ; PF00069	31.081 (46/148)	4.25E-10
Serine/threonine-protein kinase Nek5 (NEK5)	PF00069	29.204 (33/113)	5.57E-10
Cyclin-dependent kinase-like 3 (CDKL3)	PF00069	28.846 (30/104)	5.59E-10
NIMA-related kinase 2 (NEK2)	PF00069	32.090 (43/134)	5.99E-10
Serine/threonine-protein kinase ULK2 (ULK2)	PF12063 ; PF00069	33.333 (36/108)	6.46E-10
Fused homolog (STK36)	PF13646 ; PF00069	32.673 (33/101)	6.68E-10
Myosin-IIIa (MYO3A)	PF00612 ; PF00063 ; PF00069 More >>	30.464 (46/151)	7.66E-10
Serine/threonine-protein kinase ULK1 (ULK1)	PF12063 ; PF00069	35.185 (38/108)	7.82E-10
Serine/threonine-protein kinase PAK 3 (PAK3)	PF00786 ; PF00069	28.966 (42/145)	9.50E-10
Protein kinase C delta (PRKCD)	PF00130 ; PF00069 ; PF00433 More >>	28.718 (56/195)	9.62E-10
Serine/threonine-protein kinase MAK (MAK)	PF00069	34.211 (39/114)	1.03E-09
Cyclin-dependent kinase 5 (CDK5)	PF00069	31.933 (38/119)	1.06E-09
Protein kinase C theta (PRKCQ)	PF00130 ; PF00069 ; PF00433 More >>	34.000 (34/100)	1.44E-09
Serine/threonine-protein kinase PAK 6 (PAK6)	PF00786 ; PF00069	34.375 (33/96)	1.52E-09
Cyclin-dependent kinase-like 4 (CDKL4)	PF00069	28.800 (36/125)	1.87E-09
Cyclin-dependent kinase-like 1 (CDKL1)	PF00069	31.313 (31/99)	1.98E-09
Serine/threonine-protein kinase TAO2 (TAOK2)	PF00069	30.588 (52/170)	2.15E-09
MAPK/ERK kinase kinase 4 (MAP3K4)	PF19431 ; PF00069	26.452 (41/155)	2.40E-09
Protein kinase G1 (PRKG1)	PF00027 ; PF16808 ; PF00069 More >>	33.333 (39/117)	2.43E-09
Cyclin-dependent kinase 12 (CDK12)	PF00069	34.000 (34/100)	2.44E-09
Microtubule-associated serine/threonine-protein kinase 4 (MAST4)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	29.386 (67/228)	2.57E-09
Cyclin-dependent kinase-like 5 (CDKL5)	PF00069	29.348 (27/92)	2.88E-09
Mitogen-activated protein kinase 4 (MAPK4)	PF00069	39.796 (39/98)	3.17E-09
Nik-related protein kinase (NRK)	PF00780 ; PF00069	26.797 (41/153)	3.27E-09
Misshapen-like kinase 1 (MINK1)	PF00780 ; PF00069	28.571 (44/154)	3.29E-09
Ste-20-related kinase (STK39)	PF12202 ; PF00069	36.449 (39/107)	3.32E-09
Cyclin-dependent kinase 17 (CDK17)	PF12330 ; PF00069	29.167 (42/144)	3.38E-09
Unc-51 like kinase 3 (ULK3)	PF04212 ; PF00069	33.028 (36/109)	3.52E-09
Cyclin-dependent kinase 3 (CDK3)	PF00069	35.052 (34/97)	3.65E-09
Serine/threonine-protein kinase Nek9 (NEK9)	PF00069 ; PF00415	24.044 (44/183)	4.21E-09
Glycogen synthase kinase-3 beta (GSK-3B)	PF00069	28.426 (56/197)	4.43E-09
Mitogen-activated protein kinase 15 (MAPK15)	PF00069	32.143 (36/112)	5.85E-09
Stress-activated protein kinase 2a (p38 alpha)	PF00069	33.000 (33/100)	6.36E-09
Glycogen synthase kinase-3 alpha (GSK-3A)	PF00069	27.500 (44/160)	6.90E-09
Ribosomal protein S6 kinase alpha-2 (RSK2)	PF00069 ; PF00433	31.034 (36/116)	7.10E-09
Proto-oncogene serine/threonine-protein kinase mos (MOS)	PF00069	28.090 (50/178)	8.60E-09
Serine/threonine-protein kinase NLK (NLK)	PF00069	32.979 (31/94)	8.63E-09
Serine/threonine-protein kinase Nek3 (NEK3)	PF00069	30.612 (30/98)	9.25E-09
Inhibitor of nuclear factor kappa-B kinase alpha (IKKA)	PF18397 ; PF12179 ; PF00069 More >>	32.283 (41/127)	9.64E-09
Ribosomal protein S6 kinase alpha-1 (RSK1)	PF00069 ; PF00433	27.586 (32/116)	1.06E-08
MAPK/ERK kinase kinase 1 (MAP3K1)	PF00069	25.000 (41/164)	1.08E-08
Serine/threonine-protein kinase 10 (STK10)	PF00069 ; PF12474	29.221 (45/154)	1.31E-08
Serine/threonine-protein kinase Nek11 (NEK11)	PF00069	29.592 (29/98)	1.33E-08
Protein kinase C beta (PRKCB)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	30.370 (41/135)	1.54E-08
Cyclin-dependent kinase 13 (CDK13)	PF12330 ; PF00069	32.432 (36/111)	1.64E-08
Ribosomal protein S6 kinase alpha-3 (RSK3)	PF00069 ; PF00433	28.448 (33/116)	1.81E-08
Mitogen-activated protein kinase 6 (MAPK6)	PF00069	33.333 (42/126)	1.81E-08
MAP kinase p38 (MAPK12)	PF00069	34.409 (32/93)	1.91E-08
Titin (TTN)		25.541 (59/231)	1.95E-08
Receptor-interacting serine/threonine-protein kinase 3 (RIPK3)	PF00069 ; PF12721	34.161 (55/161)	2.47E-08
TRAF2 and NCK interacting kinase (TNIK)	PF00780 ; PF00069	27.922 (43/154)	2.61E-08
Testis-specific serine kinase 2 (TSSK2)	PF00069	28.058 (39/139)	2.69E-08
Polo-like kinase 1 (PLK1)	PF00069 ; PF00659	26.582 (42/158)	3.24E-08
Protein kinase N1 (PKN1)	PF02185 ; PF00069 ; PF00433 More >>	32.258 (50/155)	3.42E-08
cAMP-dependent protein kinase catalytic subunit gamma (PRKACG)	PF00069	28.467 (39/137)	3.67E-08
MAPK/ERK kinase kinase 3 (MAP3K3)	PF00564 ; PF00069	26.974 (41/152)	3.73E-08
NIMA-related kinase 6 (NEK6)	PF00069	34.066 (31/91)	5.08E-08
ERK activator kinase 2 (MEK2)	PF00069	31.683 (32/101)	5.32E-08
Calmodulin-dependent kinase II (CAMKK2)	PF00069	28.800 (36/125)	5.47E-08
Mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5)	PF00780 ; PF00069	30.833 (37/120)	5.97E-08
Polo-like kinase 4 (PLK4)	PF00069 ; PF18190 ; PF18409 More >>	26.812 (37/138)	6.14E-08
MAPK/ERK kinase kinase 2 (MAP3K2)	PF00564 ; PF00069	26.316 (40/152)	6.30E-08
Extracellular signal-regulated kinase 5 (ERK5)	PF00069	28.829 (32/111)	6.52E-08
Leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1)	PF12796 ; PF16095 ; PF00069 ; PF08477 More >>	26.087 (42/161)	6.53E-08
Cyclin-dependent kinase 1 (CDK1)	PF00069	33.010 (34/103)	6.71E-08
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	PF00069	38.636 (34/88)	7.46E-08
cAMP-dependent protein kinase catalytic subunit alpha (PRKACA)	PF00069	26.812 (37/138)	7.84E-08
Microtubule-associated serine/threonine-protein kinase 3 (MAST3)	PF08926 ; PF17820 ; PF02163 ; PF00069 More >>	31.061 (41/132)	8.46E-08
MEK kinase kinase 1 (MAP4K1)	PF00780 ; PF00069	25.455 (42/165)	8.93E-08
MEK kinase kinase 4 (MAP4K4)	PF00780 ; PF00069	32.174 (37/115)	9.10E-08
Dual specificity mitogen-activated protein kinase kinase 3 (MAP2K3)	PF00069	35.593 (42/118)	9.78E-08
Myosin-IIIb (MYO3B)	PF00612 ; PF00063 ; PF00069 More >>	28.477 (43/151)	9.99E-08
MEK kinase kinase 3 (MAP4K3)	PF00780 ; PF00069	30.833 (37/120)	1.04E-07
TAO kinase 1 (TAOK1)	PF00069	31.373 (32/102)	1.11E-07
cAMP-dependent protein kinase catalytic subunit beta (PRKACB)	PF00069	26.087 (36/138)	1.12E-07
Serine/threonine-protein kinase D2 (PRKD2)	PF00130 ; PF00069	35.398 (40/113)	1.12E-07
NIMA-related kinase 1 (NEK1)	PF00069	24.107 (27/112)	1.20E-07
Dual specificity mitogen-activated protein kinase kinase 6 (MAP2K6)	PF00069	28.313 (47/166)	1.22E-07
Stress-activated protein kinase 2b (p38 beta)	PF00069	31.000 (31/100)	1.24E-07
Serine/threonine-protein kinase PAK 5 (PAK5)	PF00786 ; PF00069	28.829 (32/111)	1.33E-07
ERK activator kinase 7 (MAP2K7)	PF00069	23.737 (47/198)	1.52E-07
Mitogen-activated protein kinase 13 (MAPK13)	PF00069	33.333 (31/93)	1.61E-07
ERK activator kinase 1 (MEK1)	PF00069	30.693 (31/101)	1.74E-07
Cyclin-dependent kinase 20 (CDK20)	PF00069	32.759 (38/116)	1.76E-07
Leucine-rich repeat kinase 2 (LRRK2)	PF16095 ; PF12799 ; PF13855 ; PF00069 ; PF08477 More >>	27.439 (45/164)	2.09E-07
Putative 3-phosphoinositide-dependent protein kinase 2 (PDPK2P)	PF00069	25.275 (23/91)	2.24E-07
cAMP-dependent protein kinase catalytic subunit PRKX (PRKX)	PF00069	27.941 (38/136)	2.35E-07
Ribosomal protein S6 kinase alpha-6 (RSK6)	PF00069 ; PF00433	27.465 (39/142)	2.42E-07
PRKR-like endoplasmic reticulum kinase (PERK)	PF00069	30.303 (30/99)	2.58E-07
Aurora kinase A (AURKA)	PF00069	28.829 (32/111)	2.81E-07
TAO kinase 3 (TAOK3)	PF00069	31.068 (32/103)	2.84E-07
Doublecortin-like kinase 2 (DCLK2)	PF03607 ; PF00069	26.590 (46/173)	2.85E-07
Cyclin-dependent kinase 16 (CDK16)	PF12330 ; PF00069	31.250 (35/112)	2.86E-07
Serine/threonine-protein kinase STK11 (STK11)	PF00069	29.032 (45/155)	3.00E-07
G protein-coupled receptor kinase 6 (GRK6)	PF00069 ; PF00615	30.172 (35/116)	3.13E-07
Phosphoinositide dependent protein kinase-1 (PDPK1)	PF14593 ; PF00069	25.510 (25/98)	3.17E-07
CaM-kinase IV kinase (CAMKK1)	PF00069	33.684 (32/95)	3.32E-07
Cyclin-dependent kinase 2 (CDK2)	PF00069	33.684 (32/95)	3.49E-07
Protein kinase D (PRKD1)	PF00130 ; PF00169 ; PF00069 More >>	32.787 (40/122)	3.74E-07
Dual specificity protein kinase TTK (MPS1)	PF00069	31.624 (37/117)	4.27E-07
Putative serine/threonine-protein kinase PRKY (PRKY)	PF00069	31.633 (31/98)	4.40E-07
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	PF18397 ; PF12179 ; PF00069 More >>	32.653 (32/98)	4.84E-07
Myosin light chain kinase 3 (MYLK3)	PF00069	28.205 (33/117)	5.43E-07
BR serine/threonine kinase 2 (BRSK2)	PF00069	31.624 (37/117)	5.93E-07
MAPK/MAK/MRK overlapping kinase (MOK)	PF00069	27.885 (29/104)	6.24E-07
Protein kinase N2 (PKN2)	PF02185 ; PF00069 ; PF00433 More >>	28.302 (60/212)	6.47E-07
Protein kinase C alpha (PRKCA)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	30.000 (30/100)	6.77E-07
G protein-coupled receptor kinase 4 (GRK4)	PF00069 ; PF00615	29.091 (32/110)	6.78E-07
Ribosomal protein S6 kinase-related protein (RSKR)	PF00069	30.000 (30/100)	7.02E-07
Ribosomal protein S6 kinase beta-1 (S6K1)	PF00069 ; PF00433	28.866 (28/97)	7.53E-07
Apoptosis signal-regulating kinase 1 (MAP3K5)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	30.208 (58/192)	8.46E-07
Serine/threonine-protein kinase 33 (STK33)	PF00069	26.667 (32/120)	9.29E-07
Myosin light chain kinase 2 (MYLK2)	PF00069	28.082 (41/146)	9.71E-07
MAP kinase signal-integrating kinase 2 (MKNK2)	PF00069	36.697 (40/109)	9.75E-07
Protein kinase C gamma (PRKCG)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	30.973 (35/113)	1.02E-06
Microtubule-associated serine/threonine-protein kinase 2 (MAST2)	PF08926 ; PF17820 ; PF00069 More >>	30.000 (60/200)	1.14E-06
Protein kinase N3 (PKN3)	PF02185 ; PF00069 ; PF00433 More >>	30.282 (43/142)	1.16E-06
Stress-activated protein kinase JNK3 (JNK3)	PF00069	31.579 (30/95)	1.18E-06
Cyclin-dependent kinase 11B (CDK11B)	PF00069	32.632 (31/95)	1.20E-06
MAP/microtubule affinity-regulating kinase 4 (MARK4)	PF02149 ; PF00069 ; PF00627 More >>	25.843 (46/178)	1.22E-06
Cyclin-dependent kinase 8 (CDK8)	PF00069	26.036 (44/169)	1.26E-06
Cytoplasmic DRAK1 (STK17A)	PF00069	30.769 (36/117)	1.32E-06
Serine/threonine-protein kinase Nek10 (NEK10)	PF00069	26.923 (35/130)	1.38E-06
PAK-4 protein kinase (PAK4)	PF00786 ; PF00069	29.204 (33/113)	1.41E-06
Cyclin-dependent kinase 11A (CDK11A)	PF00069	27.381 (46/168)	1.46E-06
Beta-adrenergic receptor kinase 1 (ADRBK1)	PF00169 ; PF00069 ; PF00615 More >>	28.070 (32/114)	1.54E-06
Cyclin-dependent kinase 18 (CDK18)	PF00069	28.099 (34/121)	1.69E-06
Stress-activated protein kinase JNK1 (JNK1)	PF00069	31.579 (30/95)	1.69E-06
Serine/threonine-protein kinase D3 (PRKD3)	PF00130 ; PF00169 ; PF00069 More >>	34.513 (39/113)	1.71E-06
RAC-beta serine/threonine-protein kinase (AKT2)	PF00169 ; PF00069 ; PF00433 More >>	26.214 (27/103)	1.80E-06
Serine/threonine-protein kinase PLK3 (PLK3)	PF00069 ; PF00659	28.829 (32/111)	1.92E-06
BR serine/threonine kinase 1 (BRSK1)	PF00069	30.769 (36/117)	1.96E-06
Ribosomal protein S6 kinase beta-2 (RPS6KB2)	PF00069 ; PF00433	24.242 (32/132)	2.08E-06
Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)	PF00069	27.891 (41/147)	2.23E-06
Microtubule-associated serine/threonine-protein kinase 1 (MAST1)	PF08926 ; PF17820 ; PF00069 More >>	31.429 (33/105)	2.43E-06
Doublecortin-like kinase 1 (DCLK1)	PF03607 ; PF00069	32.710 (35/107)	2.51E-06
Apoptosis signal-regulating kinase 2 (MAP3K6)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	34.906 (37/106)	2.60E-06
RAC-alpha serine/threonine-protein kinase (AKT1)	PF00169 ; PF00069 ; PF00433 More >>	27.723 (28/101)	2.64E-06
Cyclin-dependent kinase 15 (CDK15)	PF00069	30.108 (28/93)	3.02E-06
Eukaryotic translation initiation factor 2-alpha kinase 1 (EIF2AK1)	PF00069	30.476 (32/105)	3.16E-06
Myosin light chain kinase family member 4 (MYLK4)	PF00069	28.205 (33/117)	3.56E-06
5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)	PF16579 ; PF00069	33.333 (33/99)	3.69E-06
Testis-specific serine/threonine-protein kinase 1 (TSSK1B)	PF00069	25.714 (36/140)	3.86E-06
Serine/threonine-protein kinase pim-2 (PIM2)	PF00069	27.451 (42/153)	4.02E-06
Serine/threonine-protein kinase SBK1 (SBK1)	PF00069	28.682 (37/129)	4.32E-06
Serine/threonine-protein kinase PDIK1L (PDIK1L)	PF00069	27.523 (30/109)	4.33E-06
G protein-coupled receptor kinase 5 (GRK5)	PF00069 ; PF00615	30.303 (30/99)	5.08E-06
Serine/threonine-protein kinase H2 (PSKH2)	PF00069	26.016 (32/123)	5.09E-06
Polo-like kinase 2 (PLK2)	PF00069 ; PF00659	25.180 (35/139)	5.24E-06
Calcium/calmodulin-dependent protein kinase type II subunit beta (CAMK2B)	PF08332 ; PF00069	32.673 (33/101)	5.27E-06
Cyclin-dependent kinase 19 (CDK19)	PF00069	25.444 (43/169)	5.56E-06
Serine/threonine-protein kinase 35 (STK35)	PF00069	28.947 (33/114)	5.82E-06
NUAK family SNF1-like kinase 2 (NUAK2)	PF00069	31.034 (36/116)	6.05E-06
Stress-activated protein kinase JNK2 (JNK2)	PF00069	32.584 (29/89)	6.44E-06
Cyclin-dependent kinase 14 (CDK14)	PF00069	28.846 (30/104)	6.48E-06
Serine/threonine-protein kinase PRP4 homolog (PRPF4B)	PF00069	31.683 (32/101)	6.76E-06
Cyclin-dependent kinase 7 (CDK7)	PF00069	29.630 (32/108)	6.78E-06
Salt-inducible kinase 2 (SIK2)	PF00069	27.778 (30/108)	6.91E-06
Aurora kinase C (AURKC)	PF00069	24.242 (32/132)	7.08E-06
Serine/threonine-protein kinase MARK2 (MARK2)	PF02149 ; PF00069 ; PF00627 More >>	27.068 (36/133)	7.12E-06
Calcium/calmodulin-dependent protein kinase type II subunit gamma (CAMK2G)	PF08332 ; PF00069	28.448 (33/116)	7.32E-06
Serine/threonine-protein kinase H1 (PSKH1)	PF00069	29.565 (34/115)	7.93E-06
Death-associated protein kinase 2 (DAPK2)	PF00069	26.126 (29/111)	8.55E-06
Calcium/calmodulin-dependent protein kinase type 1G (CAMK1G)	PF00069	30.172 (35/116)	1.01E-05
RAC-gamma serine/threonine-protein kinase (AKT3)	PF00169 ; PF00069 ; PF00433 More >>	26.000 (26/100)	1.03E-05
SNF-related serine/threonine-protein kinase (SNRK)	PF00069	25.564 (34/133)	1.07E-05
Rhodopsin kinase GRK1 (GRK1)	PF00069 ; PF00615	32.292 (31/96)	1.26E-05
Testis-specific serine/threonine-protein kinase 4 (TSSK4)	PF00069	26.816 (48/179)	1.54E-05
Serine/threonine-protein kinase Sgk2 (SGK2)	PF00069 ; PF00433	32.000 (32/100)	1.57E-05
Protein kinase G2 (PRKG2)	PF00027 ; PF00069	30.357 (34/112)	1.58E-05
5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)	PF16579 ; PF00069	32.323 (32/99)	1.64E-05
Serine/threonine-protein kinase Sgk1 (SGK1)	PF00069 ; PF00433	30.303 (30/99)	1.73E-05
Protein kinase C eta type (PRKCH)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	26.786 (30/112)	1.93E-05
Serine/threonine-protein kinase cot (COT)	PF00069	28.571 (30/105)	1.95E-05
Doublecortin-like kinase 3 (DCLK3)	PF00069	29.730 (33/111)	2.17E-05
Ribosomal protein S6 kinase alpha-4 (RPS6KA4)	PF00069 ; PF00433	32.692 (34/104)	2.49E-05
Hormonally up-regulated neu tumor-associated kinase (HUNK)	PF00069	28.313 (47/166)	2.71E-05
Maternal embryonic leucine zipper kinase (MELK)	PF02149 ; PF00069	30.973 (35/113)	2.78E-05
Death-associated protein kinase 3 (DAPK3)	PF00069	24.576 (29/118)	2.99E-05
MEK kinase kinase 2 (MAP4K2)	PF00780 ; PF00069	30.526 (29/95)	3.11E-05
Mitogen-activated protein kinase kinase kinase 15 (MAP3K15)	PF19039 ; PF20309 ; PF20302 ; PF13281 ; PF00069 More >>	33.019 (35/106)	3.33E-05
Microtubule affinity regulating kinase 3 (MARK3)	PF02149 ; PF00069 ; PF00627 More >>	26.316 (35/133)	3.38E-05
CDC-like kinase 4 (CLK4)	PF00069	36.145 (30/83)	3.44E-05
Beta-adrenergic receptor kinase 2 (ADRBK2)	PF00169 ; PF00069 ; PF00615 More >>	25.862 (30/116)	3.67E-05
Protein kinase C iota (PRKCI)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	26.000 (26/100)	4.71E-05
Serine/threonine-protein kinase 17B (STK17B)	PF00069	30.189 (32/106)	4.82E-05
Salt-inducible kinase 1 (SIK1)	PF00069	32.292 (31/96)	5.11E-05
PDZ binding kinase (PBK)	PF00069	23.333 (42/180)	5.17E-05
Putative serine/threonine-protein kinase SIK1B (SIK1B)	PF00069	30.526 (29/95)	5.29E-05
Endoplasmic reticulum to nucleus signaling 1 (ERN1)	PF00069 ; PF06479	31.776 (34/107)	5.36E-05
Cyclin-dependent kinase 9 (CDK9)	PF00069	28.070 (32/114)	5.54E-05
Serine/threonine-protein kinase MARK1 (MARK1)	PF02149 ; PF00069 ; PF00627 More >>	28.205 (33/117)	5.83E-05
Testis-specific serine/threonine-protein kinase 6 (TSSK6)	PF00069	30.693 (31/101)	6.61E-05
SIK family kinase 3 (SIK3)	PF00069	29.703 (30/101)	6.67E-05
MAPK-activated protein kinase 3 (MAPKAPK3)	PF00069	24.615 (32/130)	7.30E-05
Ribosomal protein S6 kinase alpha-5 (RSK5)	PF00069 ; PF00433	26.263 (26/99)	7.35E-05
BMP-2-inducible protein kinase (BMP2K)	PF15282 ; PF00069	34.444 (31/90)	8.13E-05
Serine/threonine-protein kinase 32A (STK32A)	PF00069	29.126 (30/103)	8.34E-05
Serine/threonine-protein kinase Nek8 (NEK8)	PF00069 ; PF00415	28.125 (27/96)	1.08E-04
Omphalocele kinase 1 (NUAK1)	PF00069	29.310 (34/116)	1.38E-04
MAPK-activated protein kinase 2 (MAPKAPK2)	PF00069	25.490 (52/204)	1.39E-04
Peripheral plasma membrane protein CASK (CASK)	PF00625 ; PF02828 ; PF00595 ; PF00069 ; PF00018 More >>	26.351 (39/148)	1.39E-04
Homeodomain interacting protein kinase 2 (HIPK2)	PF00069	32.692 (34/104)	1.52E-04
Adaptor-associated kinase 1 (AAK1)	PF00069	23.684 (36/152)	1.81E-04
Calcium/calmodulin-dependent protein kinase type 1B (PNCK)	PF00069	25.466 (41/161)	1.89E-04
Serine/threonine-protein kinase 32C (STK32C)	PF00069	29.412 (30/102)	1.91E-04
Cyclin-dependent kinase 10 (CDK10)	PF00069	29.464 (33/112)	1.97E-04
Protein kinase C zeta (PRKCZ)	PF00130 ; PF00564 ; PF00069 ; PF00433 More >>	25.000 (25/100)	2.10E-04
Aurora kinase B (AURKB)	PF00069	22.302 (31/139)	2.14E-04
Serine/threonine-protein kinase NIM1 (NIM1K)	PF00069	26.804 (26/97)	2.31E-04
TBC domain-containing protein kinase-like protein (TBCK)	PF00069 ; PF00566 ; PF00581 More >>	25.333 (38/150)	2.87E-04
Homeodomain-interacting protein kinase 1 (HIPK1)	PF00069	32.692 (34/104)	3.09E-04
Death-associated protein kinase 1 (DAPK1)	PF00023 ; PF12796 ; PF13637 ; PF00531 ; PF00069 More >>	26.271 (31/118)	3.17E-04
Casein kinase I delta (CSNK1D)	PF00069	28.070 (48/171)	3.27E-04
Homeodomain-interacting protein kinase 3 (HIPK3)	PF00069	31.373 (32/102)	3.31E-04
Serine/threonine-protein kinase Sgk3 (SGK3)	PF00069 ; PF00433 ; PF00787 More >>	30.303 (30/99)	3.35E-04
Serine/threonine-protein kinase NIK (MAP3K14)	PF00069	27.350 (32/117)	3.50E-04
Dual-specificity tyrosine-phosphorylation regulated kinase 1B (DYRK1B)	PF00069	31.633 (31/98)	3.77E-04
Dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A)	PF00069	32.653 (32/98)	4.11E-04
Dual-specificity tyrosine-phosphorylation regulated kinase 3 (DYRK3)	PF00069	32.292 (31/96)	5.08E-04
Casein kinase I epsilon (CSNK1E)	PF00069	28.070 (48/171)	5.13E-04
Casein kinase II alpha prime (CSNK2A2)	PF00069	24.224 (39/161)	5.28E-04
Phosphorylase kinase testis gamma 2 (PHKG2)	PF00069	25.410 (31/122)	5.41E-04
Checkpoint kinase-1 (CHK1)	PF00069	34.375 (33/96)	5.45E-04
PAS domain-containing serine/threonine-protein kinase (PASK)	PF13426 ; PF00069	26.966 (24/89)	5.67E-04
CDC42 binding protein kinase alpha (DMPK-like alpha)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 ; PF00433 More >>	26.087 (30/115)	5.76E-04
Calcium/calmodulin-dependent protein kinase type II subunit delta (CAMK2D)	PF08332 ; PF00069	31.683 (32/101)	7.21E-04
Serine/threonine-protein kinase Chk2 (RAD53)	PF00498 ; PF00069	31.776 (34/107)	7.24E-04
Serine/threonine kinase-like domain-containing protein STKLD1 (STKLD1)	PF00069	26.667 (24/90)	7.27E-04
Calcium/calmodulin-dependent protein kinase type 1D (CAMK1D)	PF00069	27.143 (38/140)	7.91E-04
Dual-specificity tyrosine-phosphorylation regulated kinase 2 (DYRK2)	PF00069	31.132 (33/106)	1.00E-03
Activin receptor type IB (ACVR1B)	PF01064 ; PF00069 ; PF08515 More >>	29.762 (25/84)	1.00E-03
Protein kinase C epsilon (PRKCE)	PF00130 ; PF00168 ; PF00069 ; PF00433 More >>	23.214 (26/112)	2.00E-03
CDC-like kinase 1 (CLK1)	PF00069	34.940 (29/83)	2.00E-03
TGF-beta receptor type I (TGFBR1)	PF01064 ; PF00069 ; PF08515 More >>	26.207 (38/145)	2.00E-03
Serine/threonine-protein kinase MRCK beta (CDC42BPB)	PF00130 ; PF00780 ; PF08826 ; PF15796 ; PF00069 More >>	25.564 (34/133)	2.00E-03
Citron Rho-interacting kinase (CIT)	PF00780 ; PF00169 ; PF00069 More >>	29.808 (31/104)	2.00E-03
Serine/threonine-protein kinase Kist (UHMK1)	PF00069 ; PF00076	30.392 (31/102)	2.00E-03
Serine/threonine-protein kinase SBK2 (SBK2)	PF00069	26.316 (25/95)	2.00E-03
Membrane-associated kinase (PKMYT1)	PF00069	25.688 (28/109)	3.00E-03
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A)	PF08332 ; PF00069	30.693 (31/101)	4.00E-03
Casein kinase II alpha (CSNK2A1)	PF00069	22.744 (63/277)	4.00E-03
Bone morphogenetic protein receptor (BMPR2)	PF01064 ; PF00069	32.222 (29/90)	4.00E-03
Yet another novel kinase 2 (STK32B)	PF00069	30.392 (31/102)	5.00E-03
Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKBKE)	PF00069 ; PF18394 ; PF18396 More >>	25.234 (27/107)	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
Phospholipase D signaling pathway	hsa04072	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
Focal adhesion	hsa04510	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Gap junction	hsa04540	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
JAK-STAT signaling pathway	hsa04630	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Regulation of actin cytoskeleton	hsa04810	Affiliated Target
Class: Cellular Processes => Cell motility	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	34	Degree centrality	3.65E-03	Betweenness centrality	7.15E-04
Closeness centrality	2.48E-01	Radiality	1.43E+01	Clustering coefficient	2.10E-01
Neighborhood connectivity	4.97E+01	Topological coefficient	7.70E-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	[+] 17 KEGG Pathways	+
1	MAPK signaling pathway
2	Ras signaling pathway
3	Rap1 signaling pathway
4	Calcium signaling pathway
5	Cytokine-cytokine receptor interaction
6	PI3K-Akt signaling pathway
7	Focal adhesion
8	Gap junction
9	Regulation of actin cytoskeleton
10	HTLV-I infection
11	Pathways in cancer
12	MicroRNAs in cancer
13	Glioma
14	Prostate cancer
15	Melanoma
16	Central carbon metabolism in cancer
17	Choline metabolism in cancer
Panther Pathway	[+] 2 Panther Pathways	+
1	Angiogenesis
2	PDGF signaling pathway
PID Pathway	[+] 11 PID Pathways	+
1	Signaling events mediated by PTP1B
2	Beta3 integrin cell surface interactions
3	S1P3 pathway
4	Nectin adhesion pathway
5	Signaling events mediated by TCPTP
6	SHP2 signaling
7	S1P1 pathway
8	Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
9	PDGFR-beta signaling pathway
10	Validated targets of C-MYC transcriptional repression
11	PDGF receptor signaling network
Reactome	[+] 3 Reactome Pathways	+
1	PIP3 activates AKT signaling
2	Constitutive Signaling by Aberrant PI3K in Cancer
3	RAF/MAP kinase cascade
WikiPathways	[+] 8 WikiPathways	+
1	Regulation of Actin Cytoskeleton
2	MAPK Signaling Pathway
3	Osteoblast Signaling
4	Focal Adhesion
5	PIP3 activates AKT signaling
6	PDGF Pathway
7	Signaling Pathways in Glioblastoma
8	Signaling by PDGF

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5711).

REF 3

Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612.

REF 4

Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.

REF 5

REF 6

2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.

REF 7

REF 8

ClinicalTrials.gov (NCT02135107) A Double-blind Comparative Study of the Efficacy and Safety of E3810 10mg Once and Twice Daily in Maintenance Therapy for PPI Resistant Gastroesophageal Reflux Disease Patients. U.S. National Institutes of Health.

REF 9

REF 10

Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.

REF 11

ClinicalTrials.gov (NCT00570635) A Phase 2 Study of XL820 in Adults With Advanced GIST Resistant to Imatinib and/or Sunitinib. U.S. National Institutes of Health.

REF 12

MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.

REF 13

ClinicalTrials.gov (NCT02408562) Study on Tolerability of Repeat i.c.v. Administration of sNN0031 Infusion Solution in Patients With PD. U.S. National Institutes of Health.

REF 14

Anti-angiogenic and anti-tumor effects of TAK-593, a potent and selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinase. Cancer Sci. 2013Apr;104(4):486-94.

REF 15

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010224)

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000818)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007988)

REF 18

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

REF 19

E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.

REF 20

National Cancer Institute Drug Dictionary (drug id 452042).

REF 21

Company report (Neuronova)

REF 22

Biochemical characterization of TAK-593, a novel VEGFR/PDGFR inhibitor with a two-step slow binding mechanism. Biochemistry. 2011 Feb 8;50(5):738-51.

REF 23

Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.

REF 24

RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.

REF 25

Blockade of platelet-derived growth factor receptor-beta by CDP860, a humanized, PEGylated di-Fab', leads to fluid accumulation and is associated w... J Clin Oncol. 2005 Feb 10;23(5):973-81.

REF 26

Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.

REF 27

Inhibition of FLT3 and PDGFR tyrosine kinase activity by bis(benzo[b]furan-2-yl)methanones. Bioorg Med Chem. 2007 Mar 1;15(5):2187-97.

REF 28

A new series of PDGF receptor tyrosine kinase inhibitors: 3-substituted quinoline derivatives. J Med Chem. 1994 Jul 8;37(14):2129-37.

REF 29

Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase. J Med Chem. 2006 Jun 1;49(11):3101-15.

REF 30

(6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad ant... J Med Chem. 2005 Dec 29;48(26):8163-73.

REF 31

Structure-activity relationships for 1-phenylbenzimidazoles as selective ATP site inhibitors of the platelet-derived growth factor receptor. J Med Chem. 1998 Dec 31;41(27):5457-65.

REF 32

Synthesis and biological activity of N(4)-phenylsubstituted-6-(2,4-dichloro phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as vascular endo... Bioorg Med Chem. 2010 May 15;18(10):3575-87.

REF 33

A novel series of 4-phenoxyquinolines: potent and highly selective inhibitors of PDGF receptor autophosphorylation, Bioorg. Med. Chem. Lett. 7(23):2935-2940 (1997).

REF 34

Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor... J Med Chem. 2009 Jan 22;52(2):278-92.

REF 35

5,7-Dimethoxy-3-(4-pyridinyl)quinoline is a potent and selective inhibitor of human vascular beta-type platelet-derived growth factor receptor tyro... J Med Chem. 1994 Aug 19;37(17):2627-9.

REF 36

Structure-activity relationships for 5-substituted 1-phenylbenzimidazoles as selective inhibitors of the platelet-derived growth factor receptor. J Med Chem. 1999 Jul 1;42(13):2373-82.

REF 37

Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.

REF 38

Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer Res. 2005 Feb 1;65(3):957-66.

REF 39

Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol. 2000 Oct 1;60(7):885-98.

REF 40

Identification of potent and selective inhibitors of PDGF receptor autophosphorylation. J Med Chem. 2006 Apr 6;49(7):2186-92.

REF 41

A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol Cancer Ther. 2006 Nov;5(11):2634-43.

REF 42

Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. 3. Replacement of quinazoline moiety and improvement of metabolic polymorphism of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives. J Med Chem. 2003 Nov 6;46(23):4910-25.

REF 43

The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.

REF 44

Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3.

REF 45

The synthesis and SAR of new 4-(N-alkyl-N-phenyl)amino-6,7-dimethoxyquinazolines and 4-(N-alkyl-N-phenyl)aminopyrazolo[3,4-d]pyrimidines, inhibitors of CSF-1R tyrosine kinase activity, Bioorg. Med. Chem. Lett. 7(4):421-424 (1997).

REF 46

Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinas... Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8.

REF 47

REF 48

Structures of a platelet-derived growth factor/propeptide complex and a platelet-derived growth factor/receptor complex. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11307-12.

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