Target Information

Target General Infomation
Target ID
T80975
Former ID
TTDS00008
Target Name
Vascular endothelial growth factor receptor 2
Gene Name
KDR
Synonyms
VEGFR-2; VEGFR2; Fetal liver kinase 1; FLK-1; Kinase insert domain receptor; Protein-tyrosine kinase receptor flk-1; CD309; FLK1; VEGF-2 receptor; KDR
Target Type
Successful
Disease Cutaneous Melanoma [ICD10: C43-C44]
Advanced solid tumor [ICD9: 140-199; ICD10: C00-C75, C7A, C7B]
Advanced malignancies [ICD9: 140-229; ICD10: C00-C96]
Angiogenesis disorder [ICD10: I00-I99]
Alzheimer disease [ICD9: 331; ICD10: G30]
Advanced renal cell carcinoma [ICD9: 189; ICD10: C64]
Biliary cancer [ICD10: C22, C24]
Breast cancer [ICD9: 174, 175; ICD10: C50]
Breast cancer; Liver cancer [ICD9:174, 175, 140-229, 155, 203.0; ICD10: C50, C22]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21]
Cardiovascular disorder [ICD10: I00-I99]
Chronic pain [ICD9: 338.2,780; ICD10: R52.1-R52.2, G89]
Fallopian tube cancer; Ovarian cancer; Peritoneal cavity cancer [ICD9: 140-229, 158, 183, 183.2, 221.0; ICD10: C48.1, C48.2, C56, C57, D28]
Glioma; Solid tumours [ICD9: 140-199, 191; ICD10: C00-C75, C71, C7A, C7B]
Gastric cancer [ICD9: 151; ICD10: C16]
Gastric cancer; Renal cell carcinoma; Squamous cell cancer of head and neck [ICD9: 140-229, 151, 189; ICD10: C16, C64]
Gastrointestinal cancers; Advanced renal cell carcinoma [ICD9:150-159, 189; ICD10: C15-C26, C64]
Head and neck cancer [ICD9: 140-149, 140-229; ICD10: C07-C14, C32-C33]
Hepatocellular carcinoma; NSCLC; Melanoma [ICD9: 155, 162, 172; ICD10: C22.0, C33, C34, C43]
Medullary thyroid cancer [ICD9: 193; ICD10: C73]
Metastatic castration-resistant prostate cancer; Ovarian cancer [ICD9: 140-229, 183, 185; ICD10: C56, C61]
Metastatic breast cancer [ICD10: C50]
Melanoma [ICD9: 172; ICD10: C43]
Myelodysplastic syndrome; AML; Head and neck cancer; Breast cancer; Pancreatic cancer [ICD9: 140-149, 140-229, 157, 183, 205.0; ICD10: C07-C14, C25, C32, C33, C56, C92.0]
Metastatic colorectal cancer [ICD9: 153, 154; ICD10: C18-C21]
Non-small-cell lung cancer; Ovarian cancer; Solid tumours [ICD9: 140-199, 140-229, 162, 183, 210-229; ICD10: C33-C34, C56, D10-D36, D3A]
Non-small cell lung cancer [ICD10: C33-C34]
Ovarian cancer [ICD9: 183; ICD10: C56]
Renal cancer [ICD9: 140-229, 189; ICD10: C64]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Thyroid cancer; Renal cell carcinoma [ICD9: 140-229, 189, 193; ICD10: C64, C73]
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. 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.
BioChemical Class
Kinase
Target Validation
T80975
UniProt ID
P35968
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
Structure
1VR2; 1Y6A; 1Y6B; 1YWN; 2M59; 2MET; 2MEU; 2OH4; 2P2H; 2P2I; 2QU5; 2QU6; 2RL5; 2X1W; 2X1X; 2XIR; 3B8Q; 3B8R; 3BE2; 3C7Q; 3CJF; 3CJG; 3CP9; 3CPB; 3CPC; 3DTW; 3EFL; 3EWH; 3KVQ; 3S35; 3S36; 3S37; 3U6J; 3V2A; 3V6B; 3VHE; 3VHK; 3VID; 3VNT; 3VO3; 4AG8; 4AGC; 4AGD; 4ASD; 4ASE; 1VR2; 1Y6A; 1Y6B; 1YWN; 2M59; 2MET; 2MEU; 2OH4; 2P2H; 2P2I; 2QU5; 2QU6; 2RL5; 2X1W; 2X1X; 2XIR; 3B8Q; 3B8R; 3BE2; 3C7Q; 3CJF; 3CJG; 3CP9; 3CPB; 3CPC; 3DTW; 3EFL; 3EWH; 3KVQ; 3S35; 3S36;3S37; 3U6J; 3V2A; 3V6B; 3VHE; 3VHK; 3VID; 3VNT; 3VO3; 4AG8; 4AGC; 4AGD; 4ASD; 4ASE
Drugs and Mode of Action
Drug(s) Axitinib Drug Info Approved Advanced renal cell carcinoma [1], [2], [3]
Cabozantinib Drug Info Approved Medullary thyroid cancer [4], [5]
Pazopanib HCl Drug Info Approved Renal cancer [6]
Ramucirumab Drug Info Approved Gastric cancer [7], [8]
Regorafenib Drug Info Approved Metastatic colorectal cancer [1], [9]
Sorafenib Drug Info Approved Advanced renal cell carcinoma [10], [11]
Sunitinib Drug Info Approved Gastrointestinal cancers; Advanced renal cell carcinoma [12], [13], [14]
Vandetanib Drug Info Approved Solid tumours [15], [16]
YN-968D1 Drug Info Approved Breast cancer [17], [18], [19]
Brivanib Drug Info Phase 3 Breast cancer; Liver cancer [20], [21]
Cediranib Drug Info Phase 3 Fallopian tube cancer; Ovarian cancer; Peritoneal cavity cancer [22], [23]
E-3810 Drug Info Phase 3 Solid tumours [24], [25]
Fruquintinib Drug Info Phase 3 Cancer [26]
HKI-272 Drug Info Phase 3 Breast cancer [27]
Sorafenib Drug Info Phase 3 Hepatocellular carcinoma; NSCLC; Melanoma [13], [11]
Tivozanib Drug Info Phase 3 Renal cancer [28], [29]
Alacizumab pegol Drug Info Phase 2 Non-small cell lung cancer [30]
BAY-57-9352 Drug Info Phase 2 Solid tumours [31]
BMS-690514 Drug Info Phase 2 Chronic pain [32]
Cabozantinib Drug Info Phase 2 Metastatic castration-resistant prostate cancer; Ovarian cancer [4], [5]
CP-547632 Drug Info Phase 2 Non-small-cell lung cancer; Ovarian cancer; Solid tumours [33], [34]
Delphinidin Drug Info Phase 2 Cardiovascular disorder [35]
Famitinib Drug Info Phase 2 Cancer [36], [37]
RAF265 Drug Info Phase 2 Melanoma [38], [39]
Sorafenib Drug Info Phase 2 Myelodysplastic syndrome; AML; Head and neck cancer; Breast cancer; Pancreatic cancer [13], [11]
VATALANIB Drug Info Phase 2 Solid tumours [40], [41]
XL880 Drug Info Phase 2 Gastric cancer; Renal cell carcinoma; Squamous cell cancer of head and neck [42], [43]
Anti-VEGFR2 CD8 cell therapy Drug Info Phase 1/2 Cancer [44]
Elpamotide Drug Info Phase 1/2 Biliary cancer [45]
MK-2461 Drug Info Phase 1/2 Alzheimer disease [46]
OTSGC-A24 Drug Info Phase 1/2 Colorectal cancer [47]
Cabozantinib Drug Info Phase 1b Thyroid cancer; Renal cell carcinoma [4], [5]
Altiratinib Drug Info Phase 1 Solid tumours [48]
CEP-11981 Drug Info Phase 1 Solid tumours [49], [50]
CYC116 Drug Info Phase 1 Solid tumours [51]
E 7080 Drug Info Phase 1 Ovarian cancer [52]
E-7050 Drug Info Phase 1 Head and neck cancer [53], [54]
KRN633 Drug Info Phase 1 Glioma; Solid tumours [55], [56]
OSI-930 Drug Info Phase 1 Solid tumours [57], [58]
Pegdinetanib Drug Info Phase 1 Non-small cell lung cancer [59]
PF-00337210 Drug Info Phase 1 Solid tumours [60]
SU-6668 Drug Info Phase 1 Advanced solid tumor [61], [62]
Sulfatinib Drug Info Phase 1 Cancer [63]
TAK-593 Drug Info Phase 1 Cancer [64]
XL880 Drug Info Phase 1 Solid tumours [42], [43]
XL999 Drug Info Phase 1 Advanced malignancies [13]
Motesanib Drug Info Discontinued in Phase 3 Non-small cell lung cancer [65], [66]
SU-14813 Drug Info Discontinued in Phase 2 Metastatic breast cancer [67], [68]
IMC-1C11 Drug Info Discontinued in Phase 1 Cancer [69]
AG1295 Drug Info Terminated Discovery agent [70], [71]
CEP-5214 Drug Info Terminated Solid tumours [72]
Inhibitor (2-Methoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine Drug Info [73]
(3-Phenoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine Drug Info [73]
(4-Phenoxy-phenyl)-quinazolin-4-yl-amine Drug Info [74]
(5-Phenyl-oxazol-2-yl)-m-tolyl-amine Drug Info [73]
2-(1H-indazol-3-yl)-1H-benzo[d]imidazole Drug Info [75]
2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile Drug Info [73]
2-(p-toluidino)-4-phenylpyrimidine-5-carbonitrile Drug Info [76]
2-(pyrimidin-4-ylamino)thiazole-5-carbonitrile Drug Info [77]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione Drug Info [78]
3,4-diphenyl-1H-pyrrole-2,5-dione Drug Info [78]
3,6-Di-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine Drug Info [79]
3-((3-bromothiophen-2-yl)methylene)indolin-2-one Drug Info [80]
3-(1H-Indol-2-yl)-1H-quinolin-2-one Drug Info [81]
3-(4-aminophenyl)thieno[3,2-c]pyridin-4-amine Drug Info [82]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione Drug Info [78]
3-(5-Phenyl-oxazol-2-ylamino)-benzonitrile Drug Info [73]
3-(5-Thiophen-3-yl-pyridin-3-yl)-1H-indole Drug Info [83]
3-Benzimidazol-2-ylhydroquinolin-2-one Drug Info [84]
3-methyl-1H-thieno[2,3-c]pyrazole-5-carboxamide Drug Info [85]
3-phenyl-1,4-dihydroindeno[1,2-c]pyrazole Drug Info [86]
4-(4-aminophenyl)-1H-indazol-3yl-amine Drug Info [87]
4-(4-m-Tolylamino-phthalazin-1-yl)-benzamide Drug Info [88]
4-(4-p-Tolylamino-phthalazin-1-yl)-benzamide Drug Info [88]
4-(5-Phenyl-oxazol-2-ylamino)-benzenesulfonamide Drug Info [73]
4-(isoquinolin-5-yl)-N-m-tolylphthalazin-1-amine Drug Info [89]
4-(isoquinolin-5-yl)-N-o-tolylphthalazin-1-amine Drug Info [89]
4-Chloro-N-(2-chloro-benzoyl)-benzenesulfonamide Drug Info [90]
4-Chloro-N-(2-methyl-benzoyl)-benzenesulfonamide Drug Info [90]
4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide Drug Info [90]
4-Chloro-N-(4-chloro-benzoyl)-benzenesulfonamide Drug Info [90]
4-Chloro-N-(4-nitro-benzoyl)-benzenesulfonamide Drug Info [90]
4-phenyl-2-(phenylamino)pyrimidine-5-carbonitrile Drug Info [76]
5-(4-Methoxy-phenyl)-1-phenyl-1H-benzoimidazole Drug Info [91]
6-(1H-Benzoimidazol-2-yl)-benzocyclohepten-7-one Drug Info [81]
6-o-tolylquinazolin-2-amine Drug Info [92]
8-methyl-4H,7H-indolo[6,5,4-cd]indol-5-one Drug Info [80]
AAL-993 Drug Info [93]
AG-E-85378 Drug Info [94]
AG1295 Drug Info [95]
AMG-429 Drug Info [96]
AST-487 Drug Info [97]
BAY-57-9352 Drug Info [98]
BIBF-1202 Drug Info [99]
BMS-536924 Drug Info [100]
BMS-645737 Drug Info [101]
BMS-690514 Drug Info [102]
BX-795 Drug Info [103]
BX-912 Drug Info [103]
Cabozantinib Drug Info [5]
CB-676475 Drug Info [104]
Cediranib Drug Info [98], [105]
CEP-11981 Drug Info [98]
CEP-5104 Drug Info [106]
compound 13a Drug Info [107]
compound 8h Drug Info [108]
CP-547632 Drug Info [109], [98]
CYC116 Drug Info [110]
E 7080 Drug Info [52]
E-3810 Drug Info [111]
Famitinib Drug Info [36]
Fruquintinib Drug Info [112]
HKI-272 Drug Info [113]
IM-023911 Drug Info [88]
IM-094261 Drug Info [88]
IM-094882 Drug Info [89]
Indolin-2-one deriv. 4b Drug Info [114]
Isoindolinone Urea derivative Drug Info [115]
JNJ-38158471 Drug Info [96]
K-252a analogue Drug Info [116]
Ki-20227 Drug Info [117]
KRN633 Drug Info [98]
L000021649 Drug Info [79]
MG-516 Drug Info [96]
MK-2461 Drug Info [46]
Motesanib Drug Info [118], [119], [120]
N-(2,4-Dichloro-benzoyl)-benzenesulfonamide Drug Info [90]
N-(3-Bromo-benzoyl)-4-chloro-benzenesulfonamide Drug Info [90]
Pazopanib HCl Drug Info [6]
Phenyl-(5-phenyl-oxazol-2-yl)-amine Drug Info [73]
PLX-4720 Drug Info [121]
PP121 Drug Info [122]
Pyrazolo[1,5-a]pyrimidine 3G Drug Info [79]
Ro-4396686 Drug Info [123]
SEMAXINIB Drug Info [93]
SU-11652 Drug Info [124]
SU-14813 Drug Info [125], [98], [126]
SU-6668 Drug Info [127], [98]
Sulfatinib Drug Info [128]
TG-100435 Drug Info [129]
Vandetanib Drug Info [98], [105]
VATALANIB Drug Info [113]
VEGF receptor 2 kinase inhibitor I Drug Info [130]
WHI-P180 Drug Info [80]
XL999 Drug Info [131]
YN-968D1 Drug Info [132]
[3-(5-Phenyl-oxazol-2-ylamino)-phenyl]-methanol Drug Info [73]
Antagonist Altiratinib Drug Info [133]
CEP-5214 Drug Info [134]
Modulator Anti-VEGFR2 CD8 cell therapy Drug Info [44], [135]
Axitinib Drug Info [1], [2]
Brivanib Drug Info [136]
Delphinidin Drug Info [35]
E-7050 Drug Info [137]
EPI-0030 Drug Info [96]
OSI-930 Drug Info [57], [58]
Pegdinetanib Drug Info [96]
PF-00337210 Drug Info [138]
RAF265 Drug Info [139]
Ramucirumab Drug Info [7]
Regorafenib Drug Info [140]
Sorafenib Drug Info [10]
Sunitinib Drug Info [121], [12]
TAK-593 Drug Info [64], [141]
Tivozanib Drug Info [142]
XL880 Drug Info [136]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway 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 IL2 Signaling Pathway
PANTHER Pathway Angiogenesis
VEGF signaling pathway
Pathway Interaction Database 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 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 Focal Adhesion
Nifedipine Activity
Cardiac Progenitor Differentiation
Signaling by VEGF
Angiogenesis
References
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REF 5Clinical pipeline report, company report or official report of Exelixis (2011).
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REF 10Sorafenib (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.
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REF 19Clinical pipeline report, company report or official report of LSK BioPharma.
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REF 36Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
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