Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUTJGQ)

• DTT 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
• DTT Type: Successful target; [1]
• BioChemical Class: Kinase
• UniProt ID: VGFR2_HUMAN
• TTD ID: T80975
• 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
• 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.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Cytokine-cytokine receptor interaction (hsa04060)
  Endocytosis (hsa04144)
  PI3K-Akt signaling pathway (hsa04151)
  VEGF signaling pathway (hsa04370)
  Focal adhesion (hsa04510)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  VEGF binds to VEGFR leading to receptor dimerization (R-HSA-195399)
  Integrin cell surface interactions (R-HSA-216083)
  EPHA-mediated growth cone collapse (R-HSA-3928663)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  VEGFR2 mediated cell proliferation (R-HSA-5218921)
  Neurophilin interactions with VEGF and VEGFR (R-HSA-194306)

Molecular Interaction Atlas (MIA) of This DTT

13 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Axitinib	DMGVH6N	Renal cell carcinoma	2C90	Approved	[2]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[3]
Fruquintinib	DMHOSCQ	Colorectal cancer	2B91.Z	Approved	[4]
Lenvatinib	DMB1IU4	Thyroid cancer	2D10	Approved	[1]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[5]
Ramucirumab	DMWUFQ4	Gastric adenocarcinoma	2B72	Approved	[6]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[7]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[8]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[9]
Sunitinib	DMCBJSR	Acute undifferentiated leukemia		Approved	[10]
Tivozanib	DMUKC5L	Renal cell carcinoma	2C90	Approved	[11]
Vandetanib	DMRICNP	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
YN-968D1	DMMP3Y2	Breast cancer	2C60-2C65	Approved	[13]

34 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Brivanib	DM942HP	Breast cancer	2C60-2C65	Phase 3	[14]
Cediranib	DMWO5ZR	Peritoneal cavity cancer	2C51.Z	Phase 3	[12]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[15]
HKI-272	DM6QOVN	Breast cancer	2C60-2C65	Phase 3	[16]
Rivoceranib	DM13V0P	Gastric adenocarcinoma	2B72	Phase 3	[17]
Sulfatinib	DMPOTM4	Neuroendocrine cancer	2B72.1	Phase 3	[18]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[19]
Alacizumab pegol	DM3P91Z	Non-small-cell lung cancer	2C25.Y	Phase 2	[20]
BAY-57-9352	DMVA5NS	Gastric adenocarcinoma	2B72	Phase 2	[12]
BMS-690514	DMX302C	Chronic pain	MG30	Phase 2	[21]
CP-547632	DMX054A	Non-small-cell lung cancer	2C25.Y	Phase 2	[12]
Delphinidin	DMS2WIN	Cardiovascular disease	BA00-BE2Z	Phase 2	[22]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[23]
L-DOS47	DMIEZUB	Non-small-cell lung cancer	2C25.Y	Phase 2	[24]
RAF265	DMC56T4	Melanoma	2C30	Phase 2	[25]
TTAC-0001	DM6TAFE	Recurrent glioblastoma	2A00.00	Phase 2	[19]
VATALANIB	DMY0UEQ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[16]
XL880	DMHJTR2	Breast cancer	2C60-2C65	Phase 2	[14]
Anti-VEGFR2 CD8 cell therapy	DM2910G	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[26]
Elpamotide	DM5FCO4	Biliary cancer	2E92.7	Phase 1/2	[27]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[28]
OTSGC-A24	DMN0ZQ5	Colorectal cancer	2B91.Z	Phase 1/2	[29]
A168	DMJW3F4	Gastric adenocarcinoma	2B72	Phase 1	[30]
Altiratinib	DMUJCBT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[31]
CEP-11981	DMYDTJ6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
CYC116	DMUMHXT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[32]
E-7050	DMDOCNW	Head and neck cancer	2D42	Phase 1	[33]
KRN633	DMODGJU	Glioma	2A00.0	Phase 1	[12]
OSI-930	DMF2CZ9	Solid tumour/cancer	2A00-2F9Z	Phase 1	[34]
Pegdinetanib	DM0E37K	Non-small-cell lung cancer	2C25.Y	Phase 1	[19]
PF-00337210	DM5PUO0	Solid tumour/cancer	2A00-2F9Z	Phase 1	[35]
PLX-4720	DMBK9AM	Cutaneous melanoma	2C30	Phase 1	[36]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[37]
XL999	DMYS13R	Advanced malignancy	2A00-2F9Z	Phase 1	[38]

10 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Antibodie derivative 10	DMGP5AR	Angiogenesis disorder	BE2Z	Patented	[39]
Antibodie derivative 6	DMUG6YT	N. A.	N. A.	Patented	[39]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[40]
Pyrimidine derivative 12	DMMBFQH	N. A.	N. A.	Patented	[39]
Pyrimidine derivative 13	DMASGR1	N. A.	N. A.	Patented	[39]
Pyrimidine derivative 14	DM7B2XG	N. A.	N. A.	Patented	[39]
Pyrimidine derivative 4	DM8K6IS	N. A.	N. A.	Patented	[39]
Quinazoline derivative 15	DMD965S	N. A.	N. A.	Patented	[40]
Quinazoline derivative 16	DMQ704Z	N. A.	N. A.	Patented	[40]
Quinoline and quinazoline derivative 1	DMKDTO4	N. A.	N. A.	Patented	[39]

5 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Motesanib	DMZAL8C	Non-small-cell lung cancer	2C25.Y	Discontinued in Phase 3	[41]
SU-14813	DMNRW68	Breast cancer	2C60-2C65	Discontinued in Phase 2	[12]
IMC-1C11	DMQIXD2	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[42]
AG1295	DMT10C2	N. A.	N. A.	Terminated	[43]
CEP-5214	DMFRW0G	Solid tumour/cancer	2A00-2F9Z	Terminated	[44]

71 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(2-Methoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine	DMQWD75	Discovery agent	N.A.	Investigative	[45]
(3-Phenoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine	DMGYAP7	Discovery agent	N.A.	Investigative	[45]
(4-Phenoxy-phenyl)-quinazolin-4-yl-amine	DMFO8DR	Discovery agent	N.A.	Investigative	[46]
(5-Phenyl-oxazol-2-yl)-m-tolyl-amine	DM1R5SF	Discovery agent	N.A.	Investigative	[45]
2-(1H-indazol-3-yl)-1H-benzo[d]imidazole	DM0CSH8	Discovery agent	N.A.	Investigative	[47]
2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile	DMX6QMT	Discovery agent	N.A.	Investigative	[45]
2-(p-toluidino)-4-phenylpyrimidine-5-carbonitrile	DM27YTF	Discovery agent	N.A.	Investigative	[48]
2-(pyrimidin-4-ylamino)thiazole-5-carbonitrile	DMET46L	Discovery agent	N.A.	Investigative	[49]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[50]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[50]
3,6-Di-pyridin-4-yl-pyrazolo[1,5-a]pyrimidine	DMNV0EZ	Discovery agent	N.A.	Investigative	[51]
3-((3-bromothiophen-2-yl)methylene)indolin-2-one	DME3079	Discovery agent	N.A.	Investigative	[52]
3-(1H-Indol-2-yl)-1H-quinolin-2-one	DMS3JCN	Discovery agent	N.A.	Investigative	[53]
3-(4-aminophenyl)thieno[3,2-c]pyridin-4-amine	DM30GV2	Discovery agent	N.A.	Investigative	[54]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[50]
3-(5-Phenyl-oxazol-2-ylamino)-benzonitrile	DMPBLM2	Discovery agent	N.A.	Investigative	[45]
3-(5-Thiophen-3-yl-pyridin-3-yl)-1H-indole	DM9LVR5	Discovery agent	N.A.	Investigative	[55]
3-Benzimidazol-2-ylhydroquinolin-2-one	DMQXJA1	Discovery agent	N.A.	Investigative	[56]
3-methyl-1H-thieno[2,3-c]pyrazole-5-carboxamide	DMKOX0N	Discovery agent	N.A.	Investigative	[57]
3-phenyl-1,4-dihydroindeno[1,2-c]pyrazole	DMD0OZ8	Discovery agent	N.A.	Investigative	[58]
4-(4-aminophenyl)-1H-indazol-3yl-amine	DMK1IWD	Discovery agent	N.A.	Investigative	[59]
4-(4-m-Tolylamino-phthalazin-1-yl)-benzamide	DM3KCL1	Discovery agent	N.A.	Investigative	[60]
4-(4-p-Tolylamino-phthalazin-1-yl)-benzamide	DM6ESXB	Discovery agent	N.A.	Investigative	[60]
4-(5-Phenyl-oxazol-2-ylamino)-benzenesulfonamide	DM3N9O5	Discovery agent	N.A.	Investigative	[45]
4-(isoquinolin-5-yl)-N-m-tolylphthalazin-1-amine	DM8LODU	Discovery agent	N.A.	Investigative	[61]
4-(isoquinolin-5-yl)-N-o-tolylphthalazin-1-amine	DMS30HQ	Discovery agent	N.A.	Investigative	[61]
4-Chloro-N-(2-chloro-benzoyl)-benzenesulfonamide	DMVJ61A	Discovery agent	N.A.	Investigative	[62]
4-Chloro-N-(2-methyl-benzoyl)-benzenesulfonamide	DM6SI78	Discovery agent	N.A.	Investigative	[62]
4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide	DMI3OR9	Discovery agent	N.A.	Investigative	[62]
4-Chloro-N-(4-chloro-benzoyl)-benzenesulfonamide	DMTDX2S	Discovery agent	N.A.	Investigative	[62]
4-Chloro-N-(4-nitro-benzoyl)-benzenesulfonamide	DMM0TL6	Discovery agent	N.A.	Investigative	[62]
4-phenyl-2-(phenylamino)pyrimidine-5-carbonitrile	DMONKDQ	Discovery agent	N.A.	Investigative	[48]
4-[3-Hydroxyanilino]-6,7-Dimethoxyquinazoline	DMTIA27	Discovery agent	N.A.	Investigative	[52]
5-(4-Methoxy-phenyl)-1-phenyl-1H-benzoimidazole	DMCMNKA	Discovery agent	N.A.	Investigative	[63]
6-(1H-Benzoimidazol-2-yl)-benzocyclohepten-7-one	DM5RX0K	Discovery agent	N.A.	Investigative	[53]
6-o-tolylquinazolin-2-amine	DM4TX9O	Discovery agent	N.A.	Investigative	[64]
8-methyl-4H,7H-indolo[6,5,4-cd]indol-5-one	DMA28OL	Discovery agent	N.A.	Investigative	[52]
AAL-993	DM35RFH	Discovery agent	N.A.	Investigative	[8]
AG-E-85378	DM83951	Discovery agent	N.A.	Investigative	[65]
AMG-429	DME04BH	Solid tumour/cancer	2A00-2F9Z	Investigative	[19]
AST-487	DME76KU	Discovery agent	N.A.	Investigative	[66]
BIBF-1202	DMDTLSP	Discovery agent	N.A.	Investigative	[67]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[68]
BMS-645737	DMBTMO9	Discovery agent	N.A.	Investigative	[69]
BX-795	DMRIMLJ	Discovery agent	N.A.	Investigative	[70]
BX-912	DMZA45C	Discovery agent	N.A.	Investigative	[70]
CB-676475	DMXON4L	Discovery agent	N.A.	Investigative	[71]
CEP-5104	DMV43GY	Discovery agent	N.A.	Investigative	[72]
EPI-0030	DM72DO1	Solid tumour/cancer	2A00-2F9Z	Investigative	[19]
IM-023911	DMZW0YO	Discovery agent	N.A.	Investigative	[60]
IM-094261	DMTFV65	Discovery agent	N.A.	Investigative	[60]
IM-094882	DMO18YN	Discovery agent	N.A.	Investigative	[61]
Indolin-2-one deriv. 4b	DMML9AY	Discovery agent	N.A.	Investigative	[73]
Isoindolinone Urea derivative	DMQC4HV	Discovery agent	N.A.	Investigative	[74]
JNJ-38158471	DM48Y9E	Angiogenesis disorder	BE2Z	Investigative	[19]
K-252a analogue	DMCZPH4	Discovery agent	N.A.	Investigative	[75]
Ki-20227	DM9M3VC	Discovery agent	N.A.	Investigative	[76]
L000021649	DMYWD6C	Discovery agent	N.A.	Investigative	[51]
N-(2,4-Dichloro-benzoyl)-benzenesulfonamide	DMHI4Y6	Discovery agent	N.A.	Investigative	[62]
N-(3-Bromo-benzoyl)-4-chloro-benzenesulfonamide	DMOQ08F	Discovery agent	N.A.	Investigative	[62]
Phenyl-(5-phenyl-oxazol-2-yl)-amine	DMR2B4O	Discovery agent	N.A.	Investigative	[45]
PMID22765894C8h	DMH5RFU	Discovery agent	N.A.	Investigative	[77]
PMID23639540C13a	DMLXOAQ	Discovery agent	N.A.	Investigative	[78]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[79]
Pyrazolo[1,5-a]pyrimidine 3G	DMUB0EJ	Discovery agent	N.A.	Investigative	[51]
R-84	DM1MIRJ	Solid tumour/cancer	2A00-2F9Z	Investigative	[19]
Ro-4396686	DM5DMCH	Discovery agent	N.A.	Investigative	[80]
SU-11652	DMGQXN7	Discovery agent	N.A.	Investigative	[81]
TG-100435	DMIR3X2	Discovery agent	N.A.	Investigative	[82]
VEGF receptor 2 kinase inhibitor I	DMWXCYA	Discovery agent	N.A.	Investigative	[83]
[3-(5-Phenyl-oxazol-2-ylamino)-phenyl]-methanol	DMD0LCU	Discovery agent	N.A.	Investigative	[45]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rectal cancer	2C82	Rectal colon tissue	2.74E-02	0.49	1.48
Renal cancer	2C82	Kidney	7.90E-01	0.18	0.27
Alzheimer's disease	8A00.0	Entorhinal cortex	1.98E-01	0.11	0.2
Ovarian cancer	2C82	Ovarian tissue	1.18E-01	-0.29	-0.43
Liver cancer	2C82	Liver tissue	2.93E-13	-0.77	-1.4
Myelodysplastic syndrome	2C82	Bone marrow	7.93E-05	0.11	0.37
Acute myelocytic leukaemia	2C82	Bone marrow	2.27E-01	0.03	0.14
Head and neck cancer	2C82	Head and neck tissue	7.27E-04	0.26	0.31
Melanoma	2C82	Skin	1.84E-01	0.2	0.15
Thyroid cancer	2C82	Thyroid	1.50E-03	0.44	0.82
Glioma	2C82	Brainstem tissue	6.79E-01	0.05	0.19
Glioma	2C82	White matter	7.67E-01	0.61	0.61
Gastric cancer	2C82	Gastric tissue	4.05E-01	-0.21	-1
Breast cancer	2C82	Breast tissue	6.54E-27	-0.71	-0.79
Lung cancer	2C82	Lung tissue	2.37E-83	-1.61	-2.54
Psoriasis	EA90	Skin	8.32E-09	-0.33	-0.66
Retinoblastoma	2C82	Uvea	4.37E-09	-4.77	-8.72

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