Target General Infomation
Target ID
T63966
Former ID
TTDS00007
Target Name
Vascular endothelial growth factor receptor 1
Gene Name
FLT1
Synonyms
VEGFR-1; VEGFR1; Fms-like tyrosine kinase 1; FLT-1; Tyrosine-protein kinase FRT; Tyrosine-protein kinase receptor FLT; FLT; Vascular permeability factor receptor; FRT; VEGF-1 receptor; FLT1
Target Type
Clinical Trial
Disease Arteriosclerosis; Bladder cancer [ICD9:440, 188; ICD10: I70, C67]
Advanced solid tumor; Macular degeneration [ICD9:140-199, 362.5; ICD10: C00-C75, C7A, C7B, H35.3]
Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Diabetic foot ulcer [ICD9: 707; ICD10: L88-L89]
Hereditary hemorrhagic telangiectasia [ICD10: I78.0]
Idiopathic pulmonary fibrosis; Non-small cell lung cancer [ICD9:516.3; ICD10: J84.1, C33-C34]
Ovarian cancer [ICD9: 183; ICD10: C56]
Peripheral vascular disease [ICD9: 443.9; ICD10: I73.9]
Pancreatic cancer [ICD9: 140-199, 140-229, 157, 210-229; ICD10: C25]
Renal cancer [ICD9: 140-229, 189; ICD10: C64]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Receptor for VEGF, VEGFB and PGF, and has a tyrosine-protein kinase activity. The VEGF-kinase ligand/receptor signaling system plays a key role in vascular development and regulation of vascular permeability.
BioChemical Class
Kinase
Target Validation
T63966
UniProt ID
EC Number
EC 2.7.10.1
Sequence
MVSYWDTGVLLCALLSCLLLTGSSSGSKLKDPELSLKGTQHIMQAGQTLHLQCRGEAAHK
WSLPEMVSKESERLSITKSACGRNGKQFCSTLTLNTAQANHTGFYSCKYLAVPTSKKKET
ESAIYIFISDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPD
GKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVQISTPRPV
KLLRGHTLVLNCTATTPLNTRVQMTWSYPDEKNKRASVRRRIDQSNSHANIFYSVLTIDK
MQNKDKGLYTCRVRSGPSFKSVNTSVHIYDKAFITVKHRKQQVLETVAGKRSYRLSMKVK
AFPSPEVVWLKDGLPATEKSARYLTRGYSLIIKDVTEEDAGNYTILLSIKQSNVFKNLTA
TLIVNVKPQIYEKAVSSFPDPALYPLGSRQILTCTAYGIPQPTIKWFWHPCNHNHSEARC
DFCSNNEESFILDADSNMGNRIESITQRMAIIEGKNKMASTLVVADSRISGIYICIASNK
VGTVGRNISFYITDVPNGFHVNLEKMPTEGEDLKLSCTVNKFLYRDVTWILLRTVNNRTM
HYSISKQKMAITKEHSITLNLTIMNVSLQDSGTYACRARNVYTGEEILQKKEITIRDQEA
PYLLRNLSDHTVAISSSTTLDCHANGVPEPQITWFKNNHKIQQEPGIILGPGSSTLFIER
VTEEDEGVYHCKATNQKGSVESSAYLTVQGTSDKSNLELITLTCTCVAATLFWLLLTLFI
RKMKRSSSEIKTDYLSIIMDPDEVPLDEQCERLPYDASKWEFARERLKLGKSLGRGAFGK
VVQASAFGIKKSPTCRTVAVKMLKEGATASEYKALMTELKILTHIGHHLNVVNLLGACTK
QGGPLMVIVEYCKYGNLSNYLKSKRDLFFLNKDAALHMEPKKEKMEPGLEQGKKPRLDSV
TSSESFASSGFQEDKSLSDVEEEEDSDGFYKEPITMEDLISYSFQVARGMEFLSSRKCIH
RDLAARNILLSENNVVKICDFGLARDIYKNPDYVRKGDTRLPLKWMAPESIFDKIYSTKS
DVWSYGVLLWEIFSLGGSPYPGVQMDEDFCSRLREGMRMRAPEYSTPEIYQIMLDCWHRD
PKERPRFAELVEKLGDLLQANVQQDGKDYIPINAILTGNSGFTYSTPAFSEDFFKESISA
PKFNSGSSDDVRYVNAFKFMSLERIKTFEELLPNATSMFDDYQGDSSTLLASPMLKRFTW
TDSKPKASLKIDLRVTSKSKESGLSDVSRPSFCHSSCGHVSEGKRRFTYDHAELERKIAC
CSPPPDYNSVVLYSTPPI
Drugs and Mode of Action
Drug(s) Nintedanib Drug Info Approved Idiopathic pulmonary fibrosis [556264]
Ranibizumab Drug Info Approved Hereditary hemorrhagic telangiectasia [528395], [541859]
E-3810 Drug Info Phase 3 Solid tumours [524749], [542632]
Fruquintinib Drug Info Phase 3 Cancer [525024]
Nintedanib Drug Info Phase 3 Non-small cell lung cancer [524516], [524899], [541221]
Tivozanib Drug Info Phase 3 Renal cancer [522960], [541307]
Famitinib Drug Info Phase 2 Cancer [532104], [542811]
LY3012212 Drug Info Phase 2 Arteriosclerosis; Bladder cancer [548347]
Nintedanib Drug Info Phase 2 Ovarian cancer [523930], [541221]
OCV-101 Drug Info Phase 2 Pancreatic cancer [548991]
OTSGC-A24 Drug Info Phase 1/2 Colorectal cancer [523227]
CEP-11981 Drug Info Phase 1 Solid tumours [522626], [542989]
EW-A-401 Drug Info Phase 1 Peripheral vascular disease [521594]
Sulfatinib Drug Info Phase 1 Cancer [524745]
X-82 Drug Info Phase 1 Advanced solid tumor; Macular degeneration [551750]
Angiozyme Drug Info Discontinued in Phase 2 Cancer [546650]
Telbermin Drug Info Discontinued in Phase 2 Diabetic foot ulcer [536297]
Inhibitor AAL-993 Drug Info [526484]
E-3810 Drug Info [525382]
Famitinib Drug Info [532104]
Fruquintinib Drug Info [533061]
SEMAXINIB Drug Info [526484]
SU-11652 Drug Info [526575]
Sulfatinib Drug Info [550989]
Tivozanib Drug Info [541307]
Modulator Angiozyme Drug Info
CEP-11981 Drug Info [542989]
EW-A-401 Drug Info
LY3012212 Drug Info [532445]
Nintedanib Drug Info [533123]
OCV-101 Drug Info
X-82 Drug Info [550468]
Activator Telbermin Drug Info [536297]
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
HIF-1 signaling pathway
Endocytosis
PI3K-Akt signaling pathway
Focal adhesion
Transcriptional misregulation in cancer
Rheumatoid arthritis
Pathway Interaction Database Glypican 1 network
HIF-2-alpha transcription factor network
S1P3 pathway
VEGF and VEGFR signaling network
VEGFR1 specific signals
Signaling events mediated by VEGFR1 and VEGFR2
Reactome Neurophilin interactions with VEGF and VEGFR
VEGF binds to VEGFR leading to receptor dimerization
WikiPathways Focal Adhesion
Signaling by VEGF
Angiogenesis
References
Ref 521594ClinicalTrials.gov (NCT00080392) EW-A-401 to Treat Intermittent Claudication. U.S. National Institutes of Health.
Ref 522626ClinicalTrials.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 522960ClinicalTrials.gov (NCT01076010) An Extension Treatment Protocol for Subjects Who Have Participated in a Phase 3 Study of Tivozanib Versus Sorafenib in Renal Cell Carcinoma (Protocol AV-951-09-301). U.S. National Institutes of Health.
Ref 523227ClinicalTrials.gov (NCT01227772) Study of OTSGC-A24 Vaccine in Advanced Gastric Cancer. U.S. National Institutes of Health.
Ref 523930ClinicalTrials.gov (NCT01610869) Low Dose Cyclophosphamide +/-- Nintedanib in Advanced Ovarian Cancer. U.S. National Institutes of Health.
Ref 524516ClinicalTrials.gov (NCT01979952) Nintedanib Twice Daily vs Placebo in Patients Diagnosed With Idiopathic Pulmonary Fibrosis (IPF). U.S. National Institutes of Health.
Ref 524745ClinicalTrials.gov (NCT02133157) Phase I Study of Sulfatinib(HMPL-012) in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 524749ClinicalTrials.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 524899ClinicalTrials.gov (NCT02231164) LUME-Columbus: Nintedanib Plus Docetaxel in Advanced Non-small Cell Lung Cancer With Translational Research. U.S. National Institutes of Health.
Ref 525024ClinicalTrials.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 528395Ranibizumab: Phase III clinical trial results. Ophthalmol Clin North Am. 2006 Sep;19(3):361-72.
Ref 532104Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
Ref 536297Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
Ref 541221(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: 5936).
Ref 541307(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: 6058).
Ref 541859(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: 6779).
Ref 542632(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: 7649).
Ref 542811(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: 7886).
Ref 542989(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: 8189).
Ref 546650Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009459)
Ref 548347Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024862)
Ref 548991Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031248)
Ref 551750Clinical pipeline report, company report or official report of Tyrogenex.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Ref 525382E-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. doi: 10.1158/0008-5472.CAN-10-2700. Epub 2011 Jan 6.
Ref 526484J Med Chem. 2002 Dec 19;45(26):5687-93.Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors.
Ref 526575J Med Chem. 2003 Mar 27;46(7):1116-9.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 tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase.
Ref 528467Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina. 2006 Oct;26(8):859-70.
Ref 532104Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
Ref 532445Icrucumab, a fully human monoclonal antibody against the vascular endothelial growth factor receptor-1, in the treatment of patients with advanced solid malignancies: a Phase 1 study. Invest New Drugs. 2014 Apr;32(2):303-11.
Ref 533061Discovery 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 5331232014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
Ref 536297Emerging drugs for diabetic foot ulcers. Expert Opin Emerg Drugs. 2006 Nov;11(4):709-24.
Ref 541307(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: 6058).
Ref 542989(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: 8189).
Ref 549698J Clin Oncol 33, 2015 (suppl 3; abstr 65).
Ref 550468National Cancer Institute Drug Dictionary (drug id 695817).
Ref 550989Clinical pipeline report, company report or official report of Hutchison Medi Pharma.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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