Target Information

Target General Information

Target ID

T80975 (Former ID: TTDS00008)

Target Name

Vascular endothelial growth factor receptor 2 (KDR)

Synonyms

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

Gene Name

KDR

Target Type

Successful target

[1]

Disease

[+] 9 Target-related Diseases

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

Colorectal cancer [ICD-11: 2B91]

Gastrointestinal stromal tumour [ICD-11: 2B5B]

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

Renal cell carcinoma [ICD-11: 2C90]

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

Stomach cancer [ICD-11: 2B72]

Thrombocytopenia [ICD-11: 3B64]

Thyroid cancer [ICD-11: 2D10]

Function

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

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BioChemical Class

Kinase

UniProt ID

VGFR2_HUMAN

EC Number

EC 2.7.10.1

Sequence

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

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3D Structure

Click to Show 3D Structure of This Target

AlphaFold

ADReCS ID

BADD_A04520

HIT2.0 ID

T04MBA

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 12 Approved Drugs

Axitinib

Drug Info

Approved

Renal cell carcinoma

[2], [3], [4]

Cabozantinib

Drug Info

Approved

Thyroid cancer

[5], [6]

Lenvatinib

Drug Info

Approved

Thyroid cancer

[7]

Pazopanib HCl

Drug Info

Approved

Renal cell carcinoma

[8]

Ramucirumab

Drug Info

Approved

Gastric adenocarcinoma

[9], [10]

Regorafenib

Drug Info

Approved

Metastatic colorectal cancer

[11], [3]

Romiplostim

Drug Info

Approved

Thrombocytopenia

[12], [13]

Sorafenib

Drug Info

Approved

Renal cell carcinoma

[14], [15]

Sunitinib

Drug Info

Approved

Gastrointestinal stromal tumour

[16]

Tivozanib

Drug Info

Approved

Renal cell carcinoma

[17]

Vandetanib

Drug Info

Approved

Solid tumour/cancer

[18], [19]

YN-968D1

Drug Info

Approved

Breast cancer

[20], [21], [22]

Clinical Trial Drug(s)

[+] 35 Clinical Trial Drugs

Brivanib

Drug Info

Phase 3

Liver cancer

[23], [24]

Cediranib

Drug Info

Phase 3

Peritoneal cavity cancer

[25], [26]

E-3810

Drug Info

Phase 3

Solid tumour/cancer

[27], [28]

Fruquintinib

Drug Info

Phase 3

Solid tumour/cancer

[29]

HKI-272

Drug Info

Phase 3

Breast cancer

[30], [31]

Rivoceranib

Drug Info

Phase 3

Gastric adenocarcinoma

[31]

Rosiglitazone + metformin

Drug Info

Phase 3

Diabetic complication

[32]

Sulfatinib

Drug Info

Phase 3

Neuroendocrine cancer

[33]

MGCD516

Drug Info

Phase 2/3

Solid tumour/cancer

[34]

Alacizumab pegol

Drug Info

Phase 2

Non-small-cell lung cancer

[35]

BAY-57-9352

Drug Info

Phase 2

Solid tumour/cancer

[36]

BMS-690514

Drug Info

Phase 2

Chronic pain

[37]

CP-547632

Drug Info

Phase 2

Solid tumour/cancer

[38], [39]

Delphinidin

Drug Info

Phase 2

Cardiovascular disease

[40]

Famitinib

Drug Info

Phase 2

Solid tumour/cancer

[41], [42]

L-DOS47

Drug Info

Phase 2

Non-small-cell lung cancer

[31], [43]

RAF265

Drug Info

Phase 2

Melanoma

[44], [45]

TTAC-0001

Drug Info

Phase 2

Recurrent glioblastoma

[46]

VATALANIB

Drug Info

Phase 2

Solid tumour/cancer

[47], [48]

XL880

Drug Info

Phase 2

Squamous head and neck cell carcinom

[49], [50]

Anti-VEGFR2 CD8 cell therapy

Drug Info

Phase 1/2

Solid tumour/cancer

[51]

Elpamotide

Drug Info

Phase 1/2

Biliary cancer

[52]

MK-2461

Drug Info

Phase 1/2

Alzheimer disease

[53]

OTSGC-A24

Drug Info

Phase 1/2

Colorectal cancer

[54]

Altiratinib

Drug Info

Phase 1

Solid tumour/cancer

[55]

CEP-11981

Drug Info

Phase 1

Solid tumour/cancer

[56], [57]

CYC116

Drug Info

Phase 1

Solid tumour/cancer

[58]

E-7050

Drug Info

Phase 1

Head and neck cancer

[59], [60]

KRN633

Drug Info

Phase 1

Solid tumour/cancer

[61], [62]

OSI-930

Drug Info

Phase 1

Solid tumour/cancer

[63], [64]

Pegdinetanib

Drug Info

Phase 1

Non-small-cell lung cancer

[65]

PF-00337210

Drug Info

Phase 1

Solid tumour/cancer

[66]

PLX-4720

Drug Info

Phase 1

Cutaneous melanoma

[67]

TAK-593

Drug Info

Phase 1

Solid tumour/cancer

[68]

XL999

Drug Info

Phase 1

Advanced malignancy

[69]

Patented Agent(s)

[+] 1 Patented Agents

Antibodie derivative 10

Drug Info

Patented

Neoplasm

[70], [71]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

Motesanib

Drug Info

Discontinued in Phase 3

Non-small-cell lung cancer

[72], [73]

SU-14813

Drug Info

Discontinued in Phase 2

Breast cancer

[74], [75]

IMC-1C11

Drug Info

Discontinued in Phase 1

Solid tumour/cancer

[76]

CEP-5214

Drug Info

Terminated

Solid tumour/cancer

[77]

Mode of Action

[+] 4 Modes of Action

Modulator

[+] 17 Modulator drugs

Axitinib

Drug Info

[3], [4]

Ramucirumab

Drug Info

[10]

Regorafenib

Drug Info

[79]

Sorafenib

Drug Info

[15], [81]

Sunitinib

Drug Info

[82], [83]

Tivozanib

Drug Info

[17]

Brivanib

Drug Info

[87]

Delphinidin

Drug Info

[40]

RAF265

Drug Info

[98]

XL880

Drug Info

[87]

Anti-VEGFR2 CD8 cell therapy

Drug Info

[51], [99]

E-7050

Drug Info

[104]

OSI-930

Drug Info

[63], [64]

Pegdinetanib

Drug Info

[93]

PF-00337210

Drug Info

[105]

TAK-593

Drug Info

[68], [106]

EPI-0030

Drug Info

[93]

Inhibitor

[+] 104 Inhibitor drugs

Cabozantinib

Drug Info

[6], [78]

Lenvatinib

Drug Info

[1]

Pazopanib HCl

Drug Info

[8]

Romiplostim

Drug Info

[80]

Vandetanib

Drug Info

[84], [85]

YN-968D1

Drug Info

[86]

Cediranib

Drug Info

[84], [85]

E-3810

Drug Info

[88]

Fruquintinib

Drug Info

[89]

HKI-272

Drug Info

[90]

Rosiglitazone + metformin

Drug Info

[84], [91]

Sulfatinib

Drug Info

[92]

MGCD516

Drug Info

[93]

BAY-57-9352

Drug Info

[84]

BMS-690514

Drug Info

[95]

CP-547632

Drug Info

[84], [96]

Famitinib

Drug Info

[42]

VATALANIB

Drug Info

[90]

MK-2461

Drug Info

[53]

CEP-11981

Drug Info

[84]

CYC116

Drug Info

[103]

KRN633

Drug Info

[84]

PLX-4720

Drug Info

[83]

XL999

Drug Info

[107]

Pyridine derivative 18

Drug Info

[108]

Pyrimidine derivative 12

Drug Info

[70]

Pyrimidine derivative 13

Drug Info

[70]

Pyrimidine derivative 14

Drug Info

[70]

Pyrimidine derivative 4

Drug Info

[70]

Quinazoline derivative 15

Drug Info

[108]

Quinazoline derivative 16

Drug Info

[108]

Quinoline and quinazoline derivative 1

Drug Info

[70]

Motesanib

Drug Info

[109], [110], [111]

SU-14813

Drug Info

[84], [112], [113]

AG1295

Drug Info

[115]

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

Drug Info

[117]

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

Drug Info

[117]

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

Drug Info

[118]

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

Drug Info

[117]

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

Drug Info

[119]

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

Drug Info

[117]

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

Drug Info

[120]

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

Drug Info

[121]

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

Drug Info

[122]

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

Drug Info

[122]

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

Drug Info

[123]

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

Drug Info

[124]

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

Drug Info

[125]

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

Drug Info

[126]

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

Drug Info

[122]

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

Drug Info

[117]

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

Drug Info

[127]

3-Benzimidazol-2-ylhydroquinolin-2-one

Drug Info

[128]

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

Drug Info

[129]

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

Drug Info

[130]

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

Drug Info

[131]

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

Drug Info

[132]

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

Drug Info

[132]

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

Drug Info

[117]

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

Drug Info

[133]

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

Drug Info

[133]

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

Drug Info

[134]

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

Drug Info

[134]

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

Drug Info

[134]

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

Drug Info

[134]

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

Drug Info

[134]

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

Drug Info

[120]

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

Drug Info

[124]

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

Drug Info

[135]

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

Drug Info

[125]

6-o-tolylquinazolin-2-amine

Drug Info

[136]

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

Drug Info

[124]

AAL-993

Drug Info

[80]

AG-E-85378

Drug Info

[137]

AMG-429

Drug Info

[93]

AST-487

Drug Info

[138]

BIBF-1202

Drug Info

[139]

BMS-536924

Drug Info

[140]

BMS-645737

Drug Info

[141]

BX-795

Drug Info

[142]

BX-912

Drug Info

[142]

CB-676475

Drug Info

[143]

CEP-5104

Drug Info

[144]

IM-023911

Drug Info

[132]

IM-094261

Drug Info

[132]

IM-094882

Drug Info

[133]

Indolin-2-one deriv. 4b

Drug Info

[145]

Isoindolinone Urea derivative

Drug Info

[146]

JNJ-38158471

Drug Info

[93]

K-252a analogue

Drug Info

[147]

Ki-20227

Drug Info

[148]

L000021649

Drug Info

[123]

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

Drug Info

[134]

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

Drug Info

[134]

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

Drug Info

[117]

PMID22765894C8h

Drug Info

[149]

PMID23639540C13a

Drug Info

[150]

PP121

Drug Info

[151]

Pyrazolo[1,5-a]pyrimidine 3G

Drug Info

[123]

100

Ro-4396686

Drug Info

[152]

101

SU-11652

Drug Info

[153]

102

TG-100435

Drug Info

[154]

103

VEGF receptor 2 kinase inhibitor I

Drug Info

[155]

104

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

Drug Info

[117]

Antagonist

[+] 3 Antagonist drugs

Rivoceranib

Drug Info

[31]

Altiratinib

Drug Info

[102]

CEP-5214

Drug Info

[116]

Binder

[+] 1 Binder drugs

Antibodie derivative 6

Drug Info

[70]

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

Top

Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

KEGG Pathway

[+] 8 KEGG Pathways

Ras signaling pathway

Rap1 signaling pathway

Cytokine-cytokine receptor interaction

Endocytosis

PI3K-Akt signaling pathway

VEGF signaling pathway

Focal adhesion

Proteoglycans in cancer

NetPath Pathway

[+] 1 NetPath Pathways

IL2 Signaling Pathway

Panther Pathway

[+] 2 Panther Pathways

Angiogenesis

VEGF signaling pathway

PID Pathway

[+] 9 PID Pathways

HIF-2-alpha transcription factor network

Beta3 integrin cell surface interactions

Signaling events mediated by TCPTP

SHP2 signaling

S1P1 pathway

VEGF and VEGFR signaling network

Integrins in angiogenesis

Signaling events mediated by VEGFR1 and VEGFR2

Notch-mediated HES/HEY network

Reactome

[+] 6 Reactome Pathways

Neurophilin interactions with VEGF and VEGFR

VEGF binds to VEGFR leading to receptor dimerization

Integrin cell surface interactions

EPHA-mediated growth cone collapse

VEGFA-VEGFR2 Pathway

VEGFR2 mediated cell proliferation

WikiPathways

[+] 5 WikiPathways

Focal Adhesion

Nifedipine Activity

Cardiac Progenitor Differentiation

Signaling by VEGF

Angiogenesis

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.

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: 5659).

REF 3

Nat Rev Drug Discov. 2013 Feb;12(2):87-90.

REF 4

Axitinib: VEGF inhibition in advanced thyroid cancer. Lancet Oncol. 2014 Jul;15(8):e310.

REF 5

REF 6

Clinical pipeline report, company report or official report of Exelixis (2011).

REF 7

FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 208627.

REF 8

Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.

REF 9

REF 10

2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.

REF 11

REF 12

REF 13

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

REF 14

REF 15

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 16

The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.

REF 17

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

REF 18

REF 19

2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.

REF 20

REF 21

Clinical pipeline report, company report or official report of LSK BioPharma.

REF 22

ClinicalTrials.gov (NCT02426034) Study of Apatinib Tablets in the Treatment of Advanced or Metastatic Gastric Cancer. U.S. National Institutes of Health.

REF 23

REF 24

ClinicalTrials.gov (NCT01108705) Comparison of Brivanib and Best Supportive Care (BSC) With Placebo and BSC for Treatment of Liver Cancer in Asian Patients Who Have Failed Sorafenib Treatment. U.S. National Institutes of Health.

REF 25

REF 26

ClinicalTrials.gov (NCT02446600) Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. U.S. National Institutes of Health.

REF 27

REF 28

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 29

ClinicalTrials.gov (NCT02314819) A Phase III Trial Evaluating Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients RESCO). U.S. National Institutes of Health.

REF 30

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021154)

REF 31

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

REF 32

ClinicalTrials.gov (NCT00499707) Efficacy and Safety Study of Rosiglitazone/Metformin Therapy vs Rosiglitazone and Metformin in Type 2 Diabetes Subjects. U.S. National Institutes of Health.

REF 33

ClinicalTrials.gov (NCT02589821) Phase III Study of Surufatinib in Treating Advanced Pancreatic Neuroendocrine Tumors. U.S. National Institutes of Health.

REF 34

ClinicalTrials.gov (NCT04887870) Study of Sitravatinib With or Without Other Anticancer Therapies Receiving Clinical Benefit From Parent Study. U.S. National Institutes of Health.

REF 35

ClinicalTrials.gov (NCT00152477) A Study of Paclitaxel/Carboplatin With or Without CDP791 in Patients With Lung Cancer. U.S. National Institutes of Health.

REF 36

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021605)

REF 37

A novel epidermal growth factor receptor inhibitor promotes apoptosis in non-small cell lung cancer cells resistant to erlotinib. Cancer Res. 2007 Jul 1;67(13):6253-62.

REF 38

REF 39

ClinicalTrials.gov (NCT00096239) CP-547,632 in Treating Patients With Recurrent or Persistent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer. U.S. National Institutes of Health.

REF 40

Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation. Carcinogenesis. 2006 May;27(5):989-96.

REF 41

REF 42

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 43

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

REF 44

REF 45

ClinicalTrials.gov (NCT00304525) A Study to Evaluate RAF265, an Oral Drug Administered to Subjects With Locally Advanced or Metastatic Melanoma. U.S. National Institutes of Health.

REF 46

ClinicalTrials.gov (NCT03856099) TTAC-0001 Phase II Trial With Recurrent Glioblastoma Progressed on Bevacizumab. U.S. National Institutes of Health.

REF 47

REF 48

ClinicalTrials.gov (NCT00348790) Vatalanib in Treating Patients With Recurrent or Progressive Meningioma. U.S. National Institutes of Health.

REF 49

REF 50

Clinical pipeline report, company report or official report of Exelixis (2011).

REF 51

ClinicalTrials.gov (NCT01218867) CAR T Cell Receptor Immunotherapy Targeting VEGFR2 for Patients With Metastatic Cancer. U.S. National Institutes of Health.

REF 52

ClinicalTrials.gov (NCT00655785) Antiangiogenic Peptide Vaccine Therapy With Gemcitabine in Treating Patient With Pancreatic Cancer (Phase1/2). U.S. National Institutes of Health.

REF 53

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

REF 54

ClinicalTrials.gov (NCT01227772) Study of OTSGC-A24 Vaccine in Advanced Gastric Cancer. U.S. National Institutes of Health.

REF 55

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040094)

REF 56

REF 57

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

REF 58

ClinicalTrials.gov (NCT00560716) A Phase I Pharmacologic Study of CYC116, an Oral Aurora Kinase Inhibitor, in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 59

REF 60

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

REF 61

REF 62

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017407)

REF 63

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

REF 64

Inhibition of c-Kit, VEGFR-2 (KDR), and ABCG2 by analogues of OSI-930. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6495-9.

REF 65

ClinicalTrials.gov (NCT01146171) Japanese Phase 1 Study of BMS-844203 (CT322). U.S. National Institutes of Health.

REF 66

ClinicalTrials.gov (NCT01105533) A Dose Finding Study Of A New Medication, PF-00337210 That Will Possibly Decrease Blood Supply To Tumors. U.S. National Institutes of Health.

REF 67

Targeting BRAFV600E with PLX4720 displays potent antimigratory and anti-invasive activity in preclinical models of human thyroid cancer. Oncologist. 2011;16(3):296-309.

REF 68

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 69

Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.

REF 70

VEGFR-2 inhibitors and the therapeutic applications thereof: a patent review (2012-2016).Expert Opin Ther Pat. 2017 Sep;27(9):987-1004.

REF 71

Microsomal prostaglandin E2 synthase-1 inhibitors: a patent review.Expert Opin Ther Pat. 2017 Sep;27(9):1047-1059.

REF 72

REF 73

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011016)

REF 74

REF 75

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021861)

REF 76

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013121)

REF 77

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016567)

REF 78

Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.

REF 79

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

REF 80

Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.

REF 81

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.

REF 82

2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.

REF 83

In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res. 2003 Jan;9(1):327-37.

REF 84

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 85

Clinical pipeline report, company report or official report of AstraZeneca (2009).

REF 86

YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80.

REF 87

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

REF 88

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 89

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.

REF 90

Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cyst... Bioorg Med Chem. 2007 Jun 1;15(11):3635-48.

REF 91

Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies. Clin Cancer Res. 2005 Sep 1;11(17):6240-6.

REF 92

Clinical pipeline report, company report or official report of Hutchison Medi Pharma.

REF 93

REF 94

Phase I evaluation of CDP791, a PEGylated di-Fab' conjugate that binds vascular endothelial growth factor receptor 2. Clin Cancer Res. 2007 Dec 1;13(23):7113-8.

REF 95

Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci. 2010 Aug;99(8):3579-93.

REF 96

YM-359445, an orally bioavailable vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, has highly potent antitumor activity against established tumors. Clin Cancer Res. 2006 Mar 1;12(5):1630-8.

REF 97

Clinical pipeline report, company report or official report of Helix BioPharma.

REF 98

RAF265, a dual BRAF and VEGFR2 inhibitor, prevents osteoclast formation and resorption. Therapeutic implications. Invest New Drugs. 2013 Feb;31(1):200-5.

REF 99

Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17561-6.

REF 100

Clinical phase I study of elpamotide, a peptide vaccine for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. Cancer Sci. 2012 Dec;103(12):2135-8.

REF 101

J Clin Oncol 33, 2015 (suppl 3; abstr 65).

REF 102

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

REF 103

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

REF 104

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

REF 105

Inhibition of VEGFR-2 Reverses Type 1 Diabetes in NOD Mice by Abrogating Insulitis and Restoring Islet Function. Diabetes. 2013 August; 62(8): 2870-2878.

REF 106

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 107

Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Mar;29(2):153-73.

REF 108

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

REF 109

Clinical pipeline report, company report or official report of Amgen (2009).

REF 110

Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. 2009 Aug 10;27(23):3794-801.

REF 111

Axitinib for renal cell carcinoma. Expert Opin Investig Drugs. 2008 May;17(5):741-8.

REF 112

Pfizer. Product Development Pipeline. March 31 2009.

REF 113

SU14813: a novel multiple receptor tyrosine kinase inhibitor with potent antiangiogenic and antitumor activity. Mol Cancer Ther. 2006 Jul;5(7):1774-82.

REF 114

Technology evaluation: IMC-1C11, ImClone Systems. Curr Opin Mol Ther. 2001 Aug;3(4):418-24.

REF 115

Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase i... Bioorg Med Chem. 2009 Oct 15;17(20):7324-36.

REF 116

Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cell survival and migration. Blood. 2006 Aug 15;108(4):1243-50.

REF 117

Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem. 2005 Mar 10;48(5):1610-9.

REF 118

Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I. Bioorg Med Chem Lett. 2000 Oct 2;10(19):2167-70.

REF 119

Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett. 2006 Jul 1;16(13):3595-9.

REF 120

4-Aryl-5-cyano-2-aminopyrimidines as VEGF-R2 inhibitors: synthesis and biological evaluation. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3266-70.

REF 121

Potent 2-[(pyrimidin-4-yl)amine}-1,3-thiazole-5-carbonitrile-based inhibitors of VEGFR-2 (KDR) kinase. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1146-50.

REF 122

Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.

REF 123

Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharm... Bioorg Med Chem Lett. 2002 Dec 16;12(24):3537-41.

REF 124

Pharmacophore modeling and in silico screening for new KDR kinase inhibitors. Bioorg Med Chem Lett. 2007 Apr 15;17(8):2126-33.

REF 125

Optimization of the indolyl quinolinone class of KDR (VEGFR-2) kinase inhibitors: effects of 5-amido- and 5-sulphonamido-indolyl groups on pharmaco... Bioorg Med Chem Lett. 2004 Jan 19;14(2):351-5.

REF 126

Thienopyridine urea inhibitors of KDR kinase. Bioorg Med Chem Lett. 2007 Mar 1;17(5):1246-9.

REF 127

Discovery and evaluation of 3-(5-thien-3-ylpyridin-3-yl)-1H-indoles as a novel class of KDR kinase inhibitors. Bioorg Med Chem Lett. 2003 Sep 15;13(18):2973-6.

REF 128

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 129

Scaffold oriented synthesis. Part 1: Design, preparation, and biological evaluation of thienopyrazoles as kinase inhibitors. Bioorg Med Chem Lett. 2006 Jan 1;16(1):96-9.

REF 130

Hit-to-lead optimization of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of KDR kinase inhibitors. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4371-5.

REF 131

Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted ... J Med Chem. 2007 Apr 5;50(7):1584-97.

REF 132

Arylphthalazines: identification of a new phthalazine chemotype as inhibitors of VEGFR kinase. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4696-8.

REF 133

Arylphthalazines. Part 2: 1-(Isoquinolin-5-yl)-4-arylamino phthalazines as potent inhibitors of VEGF receptors I and II. Bioorg Med Chem Lett. 2006 Mar 15;16(6):1579-81.

REF 134

Acyl sulfonamide anti-proliferatives: benzene substituent structure-activity relationships for a novel class of antitumor agents. J Med Chem. 2004 Oct 21;47(22):5367-80.

REF 135

Design and synthesis of 1,5-diarylbenzimidazoles as inhibitors of the VEGF-receptor KDR. Bioorg Med Chem Lett. 2003 Aug 4;13(15):2485-8.

REF 136

Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity. J Med Chem. 2006 Sep 21;49(19):5671-86.

REF 137

Discovery of N-phenyl nicotinamides as potent inhibitors of Kdr. Bioorg Med Chem Lett. 2007 Nov 1;17(21):6003-8.

REF 138

The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 2007 Jul 15;67(14):6956-64.

REF 139

Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.

REF 140

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 141

Discovery and preclinical studies of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]t... Bioorg Med Chem Lett. 2008 May 1;18(9):2985-9.

REF 142

Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem. 2005 May 20;280(20):19867-74.

REF 143

Synthesis of a novel biotin-tagged photoaffinity probe for VEGF receptor tyrosine kinases. Bioorg Med Chem Lett. 2006 Jan 1;16(1):129-33.

REF 144

Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-linea... J Med Chem. 2008 Sep 25;51(18):5680-9.

REF 145

Identification of substituted 3-[(4,5,6, 7-tetrahydro-1H-indol-2-yl)methylene]-1,3-dihydroindol-2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rbeta tyrosine kinases. J Med Chem. 2000 Jul 13;43(14):2655-63.

REF 146

Isoindolinone ureas: a novel class of KDR kinase inhibitors. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4505-9.

REF 147

Synthesis, modeling, and in vitro activity of (3'S)-epi-K-252a analogues. Elucidating the stereochemical requirements of the 3'-sugar alcohol on tr... J Med Chem. 2005 Jun 2;48(11):3776-83.

REF 148

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 149

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

REF 150

Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52.

REF 151

Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.

REF 152

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 153

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 154

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 155

Synthesis and biological evaluations of 3-substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J Med Chem. 1998 Jul 2;41(14):2588-603.

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