Target Information

Target General Information

Top

Target ID

T70176 (Former ID: TTDC00088)

Target Name

Cyclin-dependent kinase 2 (CDK2)

Synonyms

Sin3 associated polypeptide; SIN3-associated protein; P33 protein kinase; Cell division protein kinase 2; CDKN2

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Gene Name

CDK2

Target Type

Clinical trial target

[1]

Disease

[+] 8 Target-related Diseases

Thymoma [ICD-11: 2C27]

Brain cancer [ICD-11: 2A00]

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

Lung cancer [ICD-11: 2C25]

Lymphoma [ICD-11: 2A80-2A86]

Malignant haematopoietic neoplasm [ICD-11: 2B33]

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

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

Function

Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1. Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability. Phosphorylates CDK2AP2. Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis.

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BioChemical Class

Kinase

UniProt ID

CDK2_HUMAN

EC Number

EC 2.7.11.22

Sequence

MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNH
PNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHS
HRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYY
STAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSF
PKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL

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3D Structure

Click to Show 3D Structure of This Target

PDB

HIT2.0 ID

T75H3W

Drugs and Modes of Action

Top

Clinical Trial Drug(s)

[+] 11 Clinical Trial Drugs

PHA848125

Drug Info

Phase 2

Thymic cancer

[2], [3]

R-roscovitine

Drug Info

Phase 2

Non-small-cell lung cancer

[4], [5]

Ro 31-7453

Drug Info

Phase 2

Solid tumour/cancer

[6]

TG02

Drug Info

Phase 1/2

Anaplastic astrocytoma

[8], [9]

AG-024322

Drug Info

Phase 1

Solid tumour/cancer

[13]

AT7519

Drug Info

Phase 1

Solid tumour/cancer

[14]

AZD-5438

Drug Info

Phase 1

Solid tumour/cancer

[15], [16]

CYC065

Drug Info

Phase 1

Lymphoma

[8]

PHA-793887

Drug Info

Phase 1

Solid tumour/cancer

[17]

RGB-286638

Drug Info

Phase 1

Haematological malignancy

[18], [19]

SNS-032

Drug Info

Phase 1

Solid tumour/cancer

[20], [21]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

SCH 727965

Drug Info

Discontinued in Phase 3

Acute lymphoblastic leukaemia

[22], [23], [24]

BAY 10-00394

Drug Info

Discontinued in Phase 2

Small-cell lung cancer

[25], [26]

R547

Drug Info

Discontinued in Phase 1

Advanced solid tumour

[27], [28]

ZK 304709

Drug Info

Discontinued in Phase 1

Advanced solid tumour

[29]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

INOC-005

Drug Info

Preclinical

Solid tumour/cancer

[31]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 117 Inhibitor drugs

PHA848125

Drug Info

[33], [34]

R-roscovitine

Drug Info

[13], [35], [36]

Ro 31-7453

Drug Info

[35]

AG-024322

Drug Info

[13]

AT7519

Drug Info

[38]

CYC065

Drug Info

[8]

PHA-793887

Drug Info

[17]

RGB-286638

Drug Info

[40]

SNS-032

Drug Info

[21], [41]

4-(thiazol-5-yl)-pyrimidine derivative 1

Drug Info

[42]

4-(thiazol-5-yl)-pyrimidine derivative 2

Drug Info

[42]

4-amino-3,5-di-substituted-thiazole derivative 1

Drug Info

[42]

Alkyl sulfone derivative 1

Drug Info

[42]

Aniline derivative 1

Drug Info

[42]

Diamidothiazole derivative 1

Drug Info

[42]

Diaryl amine derivative 1

Drug Info

[42]

Flavopiridol analog 1

Drug Info

[42]

Fluorinated compound 1

Drug Info

[42]

Indole-based analog 11

Drug Info

[42]

Indole-based analog 13

Drug Info

[42]

Isosteric imidazolyl pyrimidine derivative 1

Drug Info

[42]

N-(pyridin-2-yl)pyridine methylsulfone derivative 1

Drug Info

[42]

N-(pyridin-2-yl)pyrimidin-4-amine derivative 2

Drug Info

[42]

N-phenyl-pyrimidin-4-amine derivative 1

Drug Info

[42]

Naphthyridine and isoquinoline derivative 1

Drug Info

[42]

Nitrogen mustard derivative 1

Drug Info

[42]

Oxazolyl methylthiothiazole derivative 1

Drug Info

[42]

Palbociclib/ribociclib analog 1

Drug Info

[42]

PMID25991433-Compound-A1

Drug Info

[43]

PMID26161698-Compound-25

Drug Info

[42]

Pyrazolo-triazine derivative 2

Drug Info

[42]

Pyrazolo[1,5-a]-1,3,5-triazine derivative 1

Drug Info

[42]

Pyrrolo[2,3-d]pyrimidine derivative 9

Drug Info

[42]

Roscovitine derivative 1

Drug Info

[42]

SCH 727965

Drug Info

[13]

BAY 10-00394

Drug Info

[44]

R547

Drug Info

[13]

ZK 304709

Drug Info

[13]

INOC-005

Drug Info

[45]

Olomoucine

Drug Info

[46]

(2'Z,3'E)-5-Chloro-5'-chloro-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Chloro-5'-fluoro-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Chloro-5'-hydroxy-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Chloro-5'-methyl-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Fluoro-5'-chloro-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Fluoro-5'-fluoro-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Fluoro-5'-hydroxy-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Fluoro-5'-methoxy-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Nitro-5'-chloro-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Nitro-5'-fluoro-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Nitro-5'-methoxy-indirubin-3'-oxime

Drug Info

[47]

(2'Z,3'E)-5-Nitro-5'-methyl-indirubin-3'-oxime

Drug Info

[47]

1-Amino-6-Cyclohex-3-Enylmethyloxypurine

Drug Info

[48]

10Z-Hymenialdisine

Drug Info

[46]

2-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol

Drug Info

[49]

2-ANILINO-6-CYCLOHEXYLMETHOXYPURINE

Drug Info

[50], [51]

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

Drug Info

[52]

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

Drug Info

[52]

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

Drug Info

[52]

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

Drug Info

[52]

4-(2,4-Dimethyl-Thiazol-5-Yl)-Pyrimidin-2-Ylamine

Drug Info

[48]

4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol

Drug Info

[49]

4-[(6-chloropyrazin-2-yl)amino]benzenesulfonamide

Drug Info

[50]

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

Drug Info

[53]

5-hydroxynaphthalene-1-sulfonamide

Drug Info

[50]

5-nitroindirubin-3'-oxime

Drug Info

[47]

6-(3-Amino-benzyloxy)-9H-purin-2-ylamine

Drug Info

[54]

6-(3-Methyl-benzyloxy)-9H-purin-2-ylamine

Drug Info

[54]

6-(Cyclohex-3-enylmethoxy)-9H-purin-2-ylamine

Drug Info

[54]

6-CYCLOHEXYLMETHOXY-2-(3'-CHLOROANILINO) PURINE

Drug Info

[50]

6-Cyclohexylmethoxy-pyrimidine-2,4,5-triamine

Drug Info

[55]

6-O-Cyclohexylmethyl Guanine

Drug Info

[48], [56]

9-Nitropaullone

Drug Info

[46]

aloisine

Drug Info

[57]

aloisine A

Drug Info

[58]

aminopurvalanol A

Drug Info

[59]

Benzyl-(9-isopropyl-9H-purin-6-yl)-amine

Drug Info

[60]

BMS-265246

Drug Info

[61]

BMS-536924

Drug Info

[62]

BOHEMINE

Drug Info

[60]

BX-795

Drug Info

[63]

BX-912

Drug Info

[63]

Cdk1/2 inhibitor III

Drug Info

[64]

Cdk4 inhibitor III

Drug Info

[65]

CVT-313

Drug Info

[66]

Double Oxidized Cysteine

Drug Info

[48]

GW-8510

Drug Info

[67]

Indirubin-5-sulfonate

Drug Info

[46]

JNJ-7706621

Drug Info

[68]

K00024

Drug Info

[69]

Lysine Nz-Carboxylic Acid

Drug Info

[48]

MERIOLIN 1

Drug Info

[70]

MERIOLIN 2

Drug Info

[70]

MERIOLIN 3

Drug Info

[70]

MERIOLIN 4

Drug Info

[70]

MERIOLIN 5

Drug Info

[70]

MERIOLIN 6

Drug Info

[70]

MERIOLIN 8

Drug Info

[70]

N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE

Drug Info

[50]

100

N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide

Drug Info

[71]

101

N-(4-sulfamoylphenyl)-1H-indazole-3-carboxamide

Drug Info

[50]

102

N-(5-Cyclopropyl-1h-Pyrazol-3-Yl)Benzamide

Drug Info

[48]

103

N-phenyl-1H-pyrazole-3-carboxamide

Drug Info

[50]

104

NU6140

Drug Info

[72]

105

Oxindole 95

Drug Info

[46]

106

PF-228

Drug Info

[73]

107

PHA-690509

Drug Info

[74]

108

PHENYLAMINOIMIDAZO(1,2-ALPHA)PYRIDINE

Drug Info

[50]

109

PMID18986805C9b

Drug Info

[75]

110

PMID19115845C89S

Drug Info

[76]

111

Purvalanol A

Drug Info

[77]

112

PYRAZOLOPYRIDAZINE 1

Drug Info

[78]

113

PYRAZOLOPYRIDAZINE 2

Drug Info

[78]

114

RESCOVITINE

Drug Info

[79]

115

SCH-546909

Drug Info

[66]

116

SU9516

Drug Info

[46]

117

TRIAZOLOPYRIMIDINE

Drug Info

[50]

Modulator

[+] 2 Modulator drugs

TG02

Drug Info

[37]

AZD-5438

Drug Info

[39], [16]

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: Sunitinib

Ligand Info

Structure Description

CDK2 in complex with SUNITINIB

PDB:3TI1

Method

X-ray diffraction

Resolution

1.99 Å

Mutation

[80]

PDB Sequence

MENFQKVEKI

¹⁰

GEGTYGVVYK

²⁰

ARNKLTGEVV

³⁰

ALKKIRTEGV

⁴⁴

PSTAIREISL

⁵⁴

LKELNHPNIV

⁶⁴

KLLDVIHTEN

⁷⁴

KLYLVFEFLH

⁸⁴

QDLKKFMDAS

⁹⁴

ALTGIPLPLI

¹⁰⁴

KSYLFQLLQG

¹¹⁴

LAFCHSHRVL

¹²⁴

HRDLKPQNLL

¹³⁴

INTEGAIKLA

¹⁴⁴

DFGLARAFGV

¹⁵⁴

PVRTYTHEVV

¹⁶⁴

TLWYRAPEIL

¹⁷⁴

LGCKYYSTAV

¹⁸⁴

DIWSLGCIFA

¹⁹⁴

EMVTRRALFP

²⁰⁴

GDSEIDQLFR

²¹⁴

IFRTLGTPDE

²²⁴

VVWPGVTSMP

²³⁴

DYKPSFPKWA

²⁴⁴

RQDFSKVVPP

²⁵⁴

LDEDGRSLLS

²⁶⁴

QMLHYDPNKR

²⁷⁴

ISAKAALAHP

²⁸⁴

FFQDVTKPVP

²⁹⁴

HLRL

Residue

Distance (Å)

ILE10

2.841

GLY11

4.324

VAL18

4.134

ALA31

3.333

LYS33

4.498

VAL64

3.491

PHE80

3.171

GLU81

2.952

PHE82

3.605

LEU83

2.936

Residue

Distance (Å)

HIS84

3.152

GLN85

3.763

ASP86

2.558

LYS88

3.519

LYS89

3.986

ASP92

4.933

GLN131

4.187

LEU134

3.228

ALA144

4.069

ASP145

2.788

Ligand Name: Adenosine triphosphate

Ligand Info

Structure Description

Thr 160 phosphorylated CDK2 H84S, Q85M, K89D - human cyclin A3 complex with ATP

PDB:4EOJ

Method

X-ray diffraction

Resolution

1.65 Å

Mutation

Yes

[81]

PDB Sequence

GSMENFQKVE

⁸

KIGEGTYGVV

¹⁸

YKARNKLTGE

²⁸

VVALKKIRLE

⁴²

GVPSTAIREI

⁵²

SLLKELNHPN

⁶²

IVKLLDVIHT

⁷²

ENKLYLVFEF

⁸²

LSMDLKDFMD

⁹²

ASALTGIPLP

¹⁰²

LIKSYLFQLL

¹¹²

QGLAFCHSHR

¹²²

VLHRDLKPQN

¹³²

LLINTEGAIK

¹⁴²

LADFGLARAF

¹⁵²

GVPVRTYHEV

¹⁶³

VTLWYRAPEI

¹⁷³

LLGCKYYSTA

¹⁸³

VDIWSLGCIF

¹⁹³

AEMVTRRALF

²⁰³

PGDSEIDQLF

²¹³

RIFRTLGTPD

²²³

EVVWPGVTSM

²³³

PDYKPSFPKW

²⁴³

ARQDFSKVVP

²⁵³

PLDEDGRSLL

²⁶³

SQMLHYDPNK

²⁷³

RISAKAALAH

²⁸³

PFFQDVTKPV

²⁹³

PHLRL

Residue

Distance (Å)

ILE10

3.628

GLY11

3.742

GLU12

2.737

GLY13

3.394

THR14

3.566

VAL18

4.132

ALA31

3.431

LYS33

3.053

VAL64

3.791

PHE80

3.639

Residue

Distance (Å)

GLU81

2.689

PHE82

3.739

LEU83

2.985

ASP86

2.946

ASP127

4.651

LYS129

4.002

GLN131

2.988

ASN132

2.655

LEU134

3.447

ASP145

2.433

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

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
LIM domain kinase-1 (LIMK-1)	PF00412 ; PF00595 ; PF07714 More >>	28.986 (60/207)	1.08E-23
LIM domain kinase-2 (LIMK-2)	PF00412 ; PF00595 ; PF07714 More >>	30.876 (67/217)	7.89E-23
Janus kinase 1 (JAK-1)	PF18379 ; PF18377 ; PF17887 ; PF07714 More >>	31.068 (64/206)	9.31E-22
Testis-specific kinase 1 (TESK1)	PF07714	28.502 (59/207)	3.63E-21
Janus kinase 2 (JAK-2)	PF18379 ; PF18377 ; PF17887 ; PF07714 ; PF00017 More >>	32.512 (66/203)	3.97E-21
Tyrosine-protein kinase FRK (FRK)	PF07714 ; PF00017 ; PF00018 More >>	29.064 (59/203)	4.78E-21
Tyrosine-protein kinase Lyn (JTK8)	PF07714 ; PF00017 ; PF00018 More >>	27.966 (66/236)	2.78E-20
TYK2 tyrosine kinase (TYK2)	PF18379 ; PF18377 ; PF17887 ; PF07714 More >>	31.707 (65/205)	4.50E-20
TGF-beta-activated kinase 1 (MAP3K7)	PF07714	34.123 (72/211)	6.01E-20
Testis-specific kinase 2 (TESK2)	PF07714	29.208 (59/202)	1.38E-19
B lymphocyte kinase (BLK)	PF07714 ; PF00017 ; PF00018 More >>	27.381 (69/252)	3.13E-19
Renal carcinoma antigen NY-REN-64 (IRAK-4)	PF07714	34.500 (69/200)	4.58E-19
Hematopoietic cell kinase (HCK)	PF07714 ; PF00017 ; PF00018 More >>	28.185 (73/259)	5.08E-19
Tyrosine-protein kinase BRK (PTK6)	PF07714 ; PF00017 ; PF00018 More >>	29.032 (63/217)	5.31E-19
Tyrosine-protein kinase ABL1 (ABL)	PF08919 ; PF07714 ; PF00017 ; PF00018 More >>	28.634 (65/227)	2.15E-18
Proto-oncogene c-Fes (FES)	PF07714 ; PF00017	28.351 (55/194)	2.18E-18
Fyn tyrosine protein kinase (FYN)	PF07714 ; PF00017 ; PF00018 More >>	27.753 (63/227)	2.50E-18
Ephrin type-A receptor 1 (EPHA1)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	28.205 (55/195)	3.19E-18
Tyrosine-protein kinase Srms (SRMS)	PF07714 ; PF00017	26.800 (67/250)	5.16E-18
Proto-oncogene c-Src (SRC)	PF07714 ; PF00017 ; PF00018 More >>	28.700 (64/223)	7.25E-18
Mitogen-activated protein kinase kinase kinase 13 (MAP3K13)	PF07714	28.283 (56/198)	1.05E-17
Mitogen-activated protein kinase kinase kinase 12 (MAP3K12)	PF07714	29.500 (59/200)	1.06E-17
Neurotrophic tyrosine kinase ROR1 (ROR1)	PF01392 ; PF07679 ; PF00051 ; PF07714 More >>	27.103 (58/214)	1.11E-17
LCK tyrosine protein kinase (LCK)	PF07714 ; PF00017 ; PF00018 More >>	25.769 (67/260)	1.37E-17
Megakaryocyte-associated tyrosine-protein kinase (MATK)	PF07714 ; PF00017 ; PF00018 More >>	26.190 (66/252)	1.48E-17
Yes tyrosine kinase (YES)	PF07714 ; PF00017 ; PF00018 More >>	27.309 (68/249)	1.86E-17
Macrophage-stimulating protein receptor (RON)	PF07714 ; PF01403 ; PF01833 More >>	29.469 (61/207)	2.02E-17
Ephrin type-B receptor 1 (EPHB1)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	28.155 (58/206)	2.77E-17
Fibroblast growth factor receptor 4 (FGFR4)	PF07679 ; PF13927 ; PF07714 More >>	26.809 (63/235)	3.38E-17
Mixed lineage kinase 3 (MAP3K11)	PF07714 ; PF14604	31.132 (66/212)	4.18E-17
Discoidin domain-containing receptor 2 (DDR2)	PF00754 ; PF07714	26.460 (77/291)	5.75E-17
Fibroblast growth factor receptor 2 (FGFR2)	PF07679 ; PF13927 ; PF07714 More >>	26.180 (61/233)	6.84E-17
Activated CDC42 kinase 1 (ACK-1)	PF09027 ; PF11555 ; PF07714 ; PF14604 More >>	30.476 (64/210)	7.25E-17
Focal adhesion kinase 1 (FAK)	PF00373 ; PF18038 ; PF03623 ; PF07714 More >>	28.037 (60/214)	8.84E-17
Tyrosine-protein kinase ABL2 (ABL2)	PF08919 ; PF07714 ; PF00017 ; PF00018 More >>	28.497 (55/193)	1.06E-16
Muscle-specific kinase receptor (MUSK)	PF01392 ; PF07679 ; PF13927 ; PF07714 More >>	26.222 (59/225)	1.08E-16
Tyrosine-protein kinase BMX (BMX)	PF00779 ; PF00169 ; PF07714 ; PF00017 More >>	25.188 (67/266)	1.30E-16
Mixed lineage kinase 4 (MAP3K21)	PF07714 ; PF14604	28.261 (65/230)	1.94E-16
BDNF/NT-3 growth factors receptor (TrkB)	PF07679 ; PF13855 ; PF16920 ; PF01462 ; PF07714 More >>	28.708 (60/209)	4.34E-16
Fibroblast growth factor receptor 1 (FGFR1)	PF07679 ; PF00047 ; PF07714 More >>	26.695 (63/236)	4.59E-16
Tyrosine-protein kinase Fgr (FGR)	PF07714 ; PF00017 ; PF00018 More >>	28.500 (57/200)	4.80E-16
Epithelial discoidin domain receptor 1 (DDR1)	PF00754 ; PF07714	25.497 (77/302)	5.97E-16
Mixed lineage kinase 2 (MAP3K10)	PF07714 ; PF14604	29.911 (67/224)	8.52E-16
Tyrosine-protein kinase UFO (AXL)	PF00041 ; PF13927 ; PF07714 More >>	24.746 (73/295)	8.68E-16
MLK-related kinase (MLTK)	PF07714 ; PF00536	27.885 (58/208)	8.86E-16
Neurotrophic tyrosine kinase ROR2 (ROR2)	PF01392 ; PF07679 ; PF00051 ; PF07714 More >>	25.820 (63/244)	8.97E-16
Tyrosine-protein kinase ZAP-70 (ZAP-70)	PF07714 ; PF00017	29.293 (58/198)	1.32E-15
Proto-oncogene c-Fer (FER)	PF00611 ; PF07714 ; PF00017 More >>	26.400 (66/250)	1.65E-15
Serine/threonine-protein kinase TNNI3K (TNNI3K)	PF12796 ; PF13637 ; PF07714 More >>	25.547 (70/274)	1.85E-15
Titin (TTN)		28.718 (56/195)	1.94E-15
T-cell-specific kinase (ITK)	PF00779 ; PF00169 ; PF07714 ; PF00017 ; PF00018 More >>	29.557 (60/203)	2.34E-15
Fibroblast growth factor receptor 3 (FGFR3)	PF07679 ; PF13927 ; PF07714 More >>	25.641 (60/234)	2.53E-15
Janus kinase 3 (JAK-3)	PF18379 ; PF18377 ; PF17887 ; PF07714 More >>	29.907 (64/214)	5.04E-15
Ephrin type-A receptor 7 (EPHA7)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	28.856 (58/201)	6.97E-15
Ephrin type-A receptor 5 (EPHA5)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	28.571 (56/196)	7.36E-15
Receptor-interacting protein 1 (RIPK1)	PF00531 ; PF07714 ; PF12721 More >>	25.200 (63/250)	1.54E-14
Proto-oncogene c-Met (MET)	PF07714 ; PF01437 ; PF01403 ; PF01833 More >>	29.064 (59/203)	1.63E-14
Tyrosine-protein kinase TXK (TXK)	PF07714 ; PF00017 ; PF00018 More >>	24.427 (64/262)	2.06E-14
Ephrin type-A receptor 2 (EPHA2)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	30.049 (61/203)	2.24E-14
Tyrosine-protein kinase CSK (CSK)	PF07714 ; PF00017 ; PF00018 More >>	26.000 (52/200)	2.48E-14
Ephrin type-B receptor 3 (EPHB3)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	27.000 (54/200)	2.68E-14
Angiopoietin 1 receptor (TEK)	PF00041 ; PF10430 ; PF07714 More >>	27.273 (69/253)	3.05E-14
Insulin receptor (INSR)	PF00757 ; PF17870 ; PF07714 ; PF01030 More >>	24.057 (51/212)	4.03E-14
Ephrin type-A receptor 3 (EPHA3)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF07647 More >>	26.531 (52/196)	4.35E-14
Tropomyosin-related kinase A (TrkA)	PF13855 ; PF16920 ; PF07714 ; PF18613 More >>	28.505 (61/214)	4.74E-14
Insulin receptor-related protein (INSRR)	PF00757 ; PF07714 ; PF01030 More >>	26.168 (56/214)	4.79E-14
Tyrosine-protein kinase Mer (MERTK)	PF00041 ; PF00047 ; PF07714 More >>	25.792 (57/221)	5.40E-14
Inactive tyrosine-protein kinase 7 (PTK7)	PF07679 ; PF13927 ; PF07714 More >>	24.664 (55/223)	7.30E-14
Ephrin type-B receptor 4 (EPHB4)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	26.699 (55/206)	7.70E-14
NT-3 growth factor receptor (TrkC)	PF07679 ; PF00047 ; PF13855 ; PF16920 ; PF01462 ; PF07714 More >>	26.638 (61/229)	8.22E-14
Epidermal growth factor receptor (EGFR)	PF00757 ; PF14843 ; PF07714 ; PF01030 More >>	26.214 (54/206)	9.00E-14
Ephrin type-B receptor 2 (EPHB2)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	26.601 (54/203)	9.76E-14
Ephrin type-A receptor 4 (EPHA4)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF07647 More >>	26.368 (53/201)	1.49E-13
Erbb4 tyrosine kinase receptor (Erbb-4)	PF00757 ; PF14843 ; PF07714 ; PF01030 More >>	26.341 (54/205)	1.54E-13
Tyrosine-protein kinase BTK (ATK)	PF00779 ; PF00169 ; PF07714 ; PF00017 ; PF00018 More >>	27.000 (54/200)	2.02E-13
Proto-oncogene c-Ret (RET)	PF00028 ; PF07714 ; PF17756 ; PF17812 ; PF17813 More >>	25.000 (55/220)	2.74E-13
Focal adhesion kinase 2 (PTK2B)	PF00373 ; PF18038 ; PF03623 ; PF07714 More >>	26.154 (51/195)	2.86E-13
TYRO3 tyrosine kinase receptor (TYRO3)	PF00041 ; PF07679 ; PF07714 More >>	26.168 (56/214)	3.58E-13
Tyrosine-protein kinase Tec (PSCTK4)	PF00779 ; PF00169 ; PF07714 ; PF00017 ; PF00018 More >>	25.000 (49/196)	7.51E-13
Tie-1 tyrosine kinase receptor (TIE1)	PF00041 ; PF00047 ; PF07714 More >>	27.670 (57/206)	1.97E-12
Proto-oncogene c-RAF (c-RAF)	PF00130 ; PF07714 ; PF02196 More >>	24.229 (55/227)	2.84E-12
Non-receptor tyrosine-protein kinase TNK1 (TNK1)	PF07714	29.064 (59/203)	3.52E-12
Serine/threonine-protein kinase B-raf (BRAF)	PF00130 ; PF07714 ; PF02196 More >>	25.225 (56/222)	3.67E-12
Ephrin type-A receptor 8 (EPHA8)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	25.214 (59/234)	7.57E-12
Bone morphogenetic protein receptor type-1A (BMPR1A)	PF01064 ; PF07714 ; PF08515 More >>	31.250 (75/240)	7.84E-12
Proto-oncogene c-Ros (ROS1)	PF00041 ; PF07714	25.475 (67/263)	1.29E-11
Insulin-like growth factor I receptor (IGF1R)	PF00757 ; PF07714 ; PF01030 More >>	22.642 (48/212)	1.41E-11
Bone morphogenetic protein receptor type-1B (BMPR1B)	PF01064 ; PF07714 ; PF08515 More >>	27.273 (84/308)	2.88E-11
Vascular endothelial growth factor receptor 1 (FLT-1)	PF07679 ; PF00047 ; PF13927 ; PF07714 ; PF17988 More >>	32.773 (39/119)	3.70E-11
Vascular endothelial growth factor receptor 3 (FLT-4)	PF07679 ; PF13927 ; PF07714 ; PF17988 More >>	33.133 (55/166)	4.66E-11
Tyrosine-protein kinase SYK (SYK)	PF07714 ; PF00017	23.858 (47/197)	7.36E-11
Vascular endothelial growth factor receptor 2 (KDR)	PF07679 ; PF13927 ; PF07714 ; PF17988 More >>	30.968 (48/155)	3.25E-10
Platelet-derived growth factor receptor alpha (PDGFRA)	PF07679 ; PF07714	26.590 (46/173)	5.79E-10
Activin receptor-like kinase 2 (ALK-2)	PF01064 ; PF07714 ; PF08515 More >>	27.273 (60/220)	6.33E-10
Erbb2 tyrosine kinase receptor (HER2)	PF00757 ; PF14843 ; PF07714 ; PF01030 More >>	25.490 (52/204)	9.86E-10
Serine/threonine-protein kinase A-Raf (ARAF)	PF00130 ; PF07714 ; PF02196 More >>	24.779 (56/226)	1.16E-09
Dual serine/threonine and tyrosine protein kinase (DSTYK)	PF07714	25.600 (64/250)	1.20E-09
Kinase suppressor of Ras-1 (KSR1)	PF07714 ; PF13543 ; PF20406 More >>	23.113 (49/212)	2.42E-09
Serine/threonine-protein kinase LMTK3 (LMTK3)	PF07714	27.219 (46/169)	3.12E-09
Tyrosine-protein kinase STYK1 (STYK1)	PF07714	27.053 (56/207)	3.66E-09
Tyrosine-protein kinase Kit (KIT)	PF00047 ; PF07714	25.926 (49/189)	4.52E-09
Kinase suppressor of Ras 2 (KSR2)	PF07714 ; PF13543 ; PF20406 More >>	24.664 (55/223)	1.41E-08
Ephrin type-A receptor 6 (EPHA6)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF00536 More >>	22.581 (56/248)	2.10E-08
Ephrin type-B receptor 6 (EPHB6)	PF14575 ; PF01404 ; PF07699 ; PF00041 ; PF07714 ; PF07647 More >>	24.500 (49/200)	3.22E-08
Platelet-derived growth factor receptor beta (PDGFRB)	PF07679 ; PF00047 ; PF13927 ; PF07714 More >>	33.684 (32/95)	9.16E-08
Macrophage colony-stimulating factor 1 receptor (CSF1R)	PF00047 ; PF13927 ; PF07714 More >>	30.400 (38/125)	1.56E-07
Retinal guanylyl cyclase 2 (GUCY2F)	PF01094 ; PF00211 ; PF07701 ; PF07714 More >>	24.044 (44/183)	6.31E-07
Erbb3 tyrosine kinase receptor (Erbb-3)	PF00757 ; PF14843 ; PF07714 ; PF01030 More >>	25.616 (52/203)	6.56E-07
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)	PF00619 ; PF07714	25.238 (53/210)	1.06E-06
Activin receptor type-1C (ACVR1C)	PF01064 ; PF07714 ; PF08515 More >>	27.313 (62/227)	1.22E-06
ALK tyrosine kinase receptor (ALK)	PF12810 ; PF00629 ; PF07714 More >>	23.013 (55/239)	2.76E-06
Fms-like tyrosine kinase 3 (FLT-3)	PF00047 ; PF07714	24.427 (32/131)	3.05E-06
Serine/threonine-protein kinase LMTK2 (LMTK2)	PF07714	25.683 (47/183)	4.12E-06
Ankyrin repeat and protein kinase domain-containing protein 1 (ANKK1)	PF12796 ; PF13637 ; PF07714 More >>	22.260 (65/292)	6.65E-06
TGF-beta receptor type II (TGFBR2)	PF08917 ; PF07714	24.299 (52/214)	7.02E-06
Activin receptor-like kinase-1 (ACVRL1)	PF07714 ; PF08515	28.378 (63/222)	8.99E-06
Guanylyl cyclase C (GUCY2C)	PF00211 ; PF07714	24.277 (42/173)	2.44E-05
Ephrin type-A receptor 10 (EPHA10)	PF14575 ; PF01404 ; PF00041 ; PF07714 ; PF00536 More >>	26.633 (53/199)	3.24E-05
Tyrosine-protein kinase RYK (RYK)	PF07714 ; PF02019	23.237 (56/241)	3.50E-05
Nuclear receptor-binding protein (NRBP1)	PF07714	23.320 (59/253)	1.07E-04
Soluble guanylyl cyclase (GUCY2D)	PF01094 ; PF00211 ; PF07701 ; PF07714 More >>	27.778 (55/198)	2.25E-04
Serine/threonine-protein kinase LMTK1 (AATK)	PF07714	23.039 (47/204)	4.00E-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
FoxO signaling pathway	hsa04068	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Cell cycle	hsa04110	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Oocyte meiosis	hsa04114	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
p53 signaling pathway	hsa04115	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
PI3K-Akt signaling pathway	hsa04151	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Cellular senescence	hsa04218	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Progesterone-mediated oocyte maturation	hsa04914	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	74	Degree centrality	7.95E-03	Betweenness centrality	4.53E-03
Closeness centrality	2.60E-01	Radiality	1.45E+01	Clustering coefficient	1.78E-01
Neighborhood connectivity	4.41E+01	Topological coefficient	4.18E-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	[+] 14 KEGG Pathways	+
1	FoxO signaling pathway
2	Cell cycle
3	Oocyte meiosis
4	p53 signaling pathway
5	PI3K-Akt signaling pathway
6	Progesterone-mediated oocyte maturation
7	Hepatitis B
8	Measles
9	Herpes simplex infection
10	Epstein-Barr virus infection
11	Pathways in cancer
12	Viral carcinogenesis
13	Prostate cancer
14	Small cell lung cancer
NetPath Pathway	[+] 1 NetPath Pathways	+
1	TCR Signaling Pathway
Panther Pathway	[+] 2 Panther Pathways	+
1	p53 pathway
2	p53 pathway feedback loops 2
PID Pathway	[+] 12 PID Pathways	+
1	Regulation of nuclear SMAD2/3 signaling
2	Signaling events mediated by PRL
3	p73 transcription factor network
4	E2F transcription factor network
5	ATR signaling pathway
6	mTOR signaling pathway
7	IL2-mediated signaling events
8	FoxO family signaling
9	FOXM1 transcription factor network
10	BARD1 signaling events
11	p53 pathway
12	Regulation of retinoblastoma protein
Reactome	[+] 15 Reactome Pathways	+
1	G0 and Early G1
2	Activation of ATR in response to replication stress
3	Regulation of APC/C activators between G1/S and early anaphase
4	SCF(Skp2)-mediated degradation of p27/p21
5	Senescence-Associated Secretory Phenotype (SASP)
6	DNA Damage/Telomere Stress Induced Senescence
7	Processing of DNA double-strand break ends
8	G2 Phase
9	Orc1 removal from chromatin
10	Cyclin E associated events during G1/S transition
11	Cyclin A/B1 associated events during G2/M transition
12	p53-Dependent G1 DNA Damage Response
13	Cyclin A:Cdk2-associated events at S phase entry
14	Meiotic recombination
15	Factors involved in megakaryocyte development and platelet production
WikiPathways	[+] 27 WikiPathways	+
1	DNA Damage Response
2	ID signaling pathway
3	DNA Replication
4	G1 to S cell cycle control
5	M/G1 Transition
6	S Phase
7	Meiotic Recombination
8	Aryl Hydrocarbon Receptor
9	ATM Signaling Pathway
10	Retinoblastoma (RB) in Cancer
11	Spinal Cord Injury
12	Integrated Pancreatic Cancer Pathway
13	Oncostatin M Signaling Pathway
14	Prostate Cancer
15	Signaling Pathways in Glioblastoma
16	TSH signaling pathway
17	Integrated Breast Cancer Pathway
18	Integrated Cancer pathway
19	Synthesis of DNA
20	Regulation of DNA replication
21	Mitotic G2-G2/M phases
22	Mitotic G1-G1/S phases
23	Factors involved in megakaryocyte development and platelet production
24	Cell Cycle
25	APC/C-mediated degradation of cell cycle proteins
26	Cell Cycle Checkpoints
27	miRNA Regulation of DNA Damage Response

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

Agreement signed with Prostagenics to develop prostate cancer treatment. Innovate Oncology, Inc. 2005.

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: 7938).

REF 3

ClinicalTrials.gov (NCT01011439) Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma. U.S. National Institutes of Health.

REF 4

REF 5

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010117)

REF 6

A phase 2 study of oral MKC-1, an inhibitor of importin-beta, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer. Invest New Drugs. 2012 Aug;30(4):1614-20.

REF 7

ClinicalTrials.gov (NCT04541225) Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors. U.S.National Institutes of Health.

REF 8

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

REF 9

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

REF 10

ClinicalTrials.gov (NCT04553133) PF-07104091 as a Single Agent and in Combination Therapy. U.S. National Institutes of Health.

REF 11

ClinicalTrials.gov (NCT03690154) A Phase 1 Study to Evaluate FN-1501 Monotherapy in Patients With Advanced Solid Tumors and R/R AML. U.S. National Institutes of Health.

REF 12

ClinicalTrials.gov (NCT05304962) First-in-Human, Escalating Oral Dose Study of RGT-419B Given Alone and With Endocrine Therapy in Subjects With Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Advanced/Metastatic Breast Cancer. U.S.National Institutes of Health.

REF 13

Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.

REF 14

ClinicalTrials.gov (NCT02503709) Onalespib and CDKI AT7519 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery in National Cancer Institute (NCI).

REF 15

REF 16

AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66.

REF 17

A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70.

REF 18

REF 19

ClinicalTrials.gov (NCT01168882) Safety and Tolerability of RGB-286638 in Patients With Selected, Relapsed or Refractory Hematological Malignancies. U.S. National Institutes of Health.

REF 20

REF 21

Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.

REF 22

REF 23

Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015 Jan 15;125(3):443-8.

REF 24

Cyclin-dependent kinase inhibitor Dinaciclib (SCH727965) inhibits pancreatic cancer growth and progression in murine xenograft models. Cancer Biol Ther. 2011 Oct 1;12(7):598-609.

REF 25

REF 26

BAY 1000394, a novel cyclin-dependent kinase inhibitor, with potent antitumor activity in mono- and in combination treatment upon oral application. Mol Cancer Ther. 2012 Oct;11(10):2265-73.

REF 27

REF 28

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018924)

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022386)

REF 30

Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.

REF 31

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022337)

REF 32

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014130)

REF 33

Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.

REF 34

The cyclin-dependent kinase inhibitor PHA-848125 suppresses the in vitro growth of human melanomas sensitive or resistant to temozolomide, and shows synergistic effects in combination with this triazene compound. Pharmacol Res. 2010 May;61(5):437-48.

REF 35

A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.

REF 36

Cdk2 plays a critical role in hepatocyte cell cycle progression and survival in the setting of cyclin D1 expression in vivo. Cell Cycle. 2009 Sep 1;8(17):2802-9.

REF 37

Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.

REF 38

Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009 Feb;8(2):324-32.

REF 39

AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells.Int J Radiat Oncol Biol Phys.2012 Nov 15;84(4):e507-14.

REF 40

Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.

REF 41

Development of cell-cycle inhibitors for cancer therapy. Curr Oncol. 2009 Mar;16(2):36-43.

REF 42

Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.

REF 43

c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.

REF 44

National Cancer Institute Drug Dictionary (drug id 770319).

REF 45

What are next generation innovative therapeutic targets. J Pharmacol Exp Ther. 2009 Jul;330(1):304-15.

REF 46

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