Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T80782
(Former ID: TTDC00334)
|
|||||
Target Name |
VEGFR1 messenger RNA (VEGFR1 mRNA)
|
|||||
Synonyms |
Vascular permeability factor receptor (mRNA); VEGFR1 (mRNA); VEGFR-1 (mRNA); VEGF-1 receptor (mRNA); Tyrosine-protein kinase receptor FLT (mRNA); Tyrosine-protein kinase FRT (mRNA); Fms-like tyrosine kinase 1 (mRNA); FRT (mRNA); FLT (mRNA)
Click to Show/Hide
|
|||||
Gene Name |
FLT1
|
|||||
Target Type |
Successful target
|
[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Thrombocytopenia [ICD-11: 3B64] | |||||
Function |
May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Likewise, isoforms lacking a transmembrane domain, such as isoform 2, isoform 3 and isoform 4, may function as decoy receptors for VEGFA. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Isoform 1 phosphorylates PLCG. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1. Isoform 7 has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion.
Click to Show/Hide
|
|||||
BioChemical Class |
mRNA target
|
|||||
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 Click to Show/Hide
|
Drugs and Modes of Action | Top | |||||
---|---|---|---|---|---|---|
Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Romiplostim | Drug Info | Approved | Thrombocytopenia | [2], [3] | |
Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
1 | VATALANIB | Drug Info | Phase 2 | Solid tumour/cancer | [4], [5] | |
2 | MK-2461 | Drug Info | Phase 1/2 | Alzheimer disease | [6] | |
3 | Sirna-027 | Drug Info | Phase 1/2 | Exudative age-related macular degeneration | [7] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 28 Inhibitor drugs | + | ||||
1 | Romiplostim | Drug Info | [1] | |||
2 | VATALANIB | Drug Info | [8] | |||
3 | MK-2461 | Drug Info | [6] | |||
4 | (2-Methoxy-phenyl)-(5-phenyl-oxazol-2-yl)-amine | Drug Info | [10] | |||
5 | (5-Phenyl-oxazol-2-yl)-m-tolyl-amine | Drug Info | [10] | |||
6 | 2-(5-Phenyl-oxazol-2-ylamino)-benzonitrile | Drug Info | [10] | |||
7 | 3-(5-Phenyl-oxazol-2-ylamino)-benzonitrile | Drug Info | [10] | |||
8 | 4-(5-Phenyl-oxazol-2-ylamino)-benzenesulfonamide | Drug Info | [10] | |||
9 | 4-(isoquinolin-5-yl)-N-m-tolylphthalazin-1-amine | Drug Info | [11] | |||
10 | 4-(isoquinolin-5-yl)-N-o-tolylphthalazin-1-amine | Drug Info | [11] | |||
11 | 4-Chloro-N-(3-chloro-benzoyl)-benzenesulfonamide | Drug Info | [12] | |||
12 | 4-Chloro-N-(4-chloro-benzoyl)-benzenesulfonamide | Drug Info | [12] | |||
13 | 4-Chloro-N-(4-nitro-benzoyl)-benzenesulfonamide | Drug Info | [12] | |||
14 | AAL-993 | Drug Info | [8] | |||
15 | CB-676475 | Drug Info | [13] | |||
16 | Cdk1/2 inhibitor III | Drug Info | [14] | |||
17 | C[homoPhe-Hca-Glu-Gly-Leu-Glu-Glu]-NH2 | Drug Info | [15] | |||
18 | C[YYAEGLEE]-NH2 | Drug Info | [16] | |||
19 | C[YYDEGLEE]-NH2 | Drug Info | [16] | |||
20 | C[YYDEKLEE]-NH2 | Drug Info | [16] | |||
21 | IM-094882 | Drug Info | [11] | |||
22 | LYCOGARUBIN B | Drug Info | [17] | |||
23 | N-(2,4-Dichloro-benzoyl)-benzenesulfonamide | Drug Info | [12] | |||
24 | N-(3-Bromo-benzoyl)-4-chloro-benzenesulfonamide | Drug Info | [12] | |||
25 | N3-GHQMFYYPra-NH2 | Drug Info | [18] | |||
26 | Phenyl-(5-phenyl-oxazol-2-yl)-amine | Drug Info | [10] | |||
27 | PMID17935989C25 | Drug Info | [19] | |||
28 | PMID22765894C8h | Drug Info | [20] |
Cell-based Target Expression Variations | Top | |||||
---|---|---|---|---|---|---|
Cell-based Target Expression Variations |
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 |
Target Profiles in Patients | Top | |||||
---|---|---|---|---|---|---|
Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
---|---|---|---|---|---|---|
KEGG Pathway | [+] 9 KEGG Pathways | + | ||||
1 | Ras signaling pathway | |||||
2 | Rap1 signaling pathway | |||||
3 | Cytokine-cytokine receptor interaction | |||||
4 | HIF-1 signaling pathway | |||||
5 | Endocytosis | |||||
6 | PI3K-Akt signaling pathway | |||||
7 | Focal adhesion | |||||
8 | Transcriptional misregulation in cancer | |||||
9 | Rheumatoid arthritis | |||||
PID Pathway | [+] 6 PID Pathways | + | ||||
1 | Glypican 1 network | |||||
2 | HIF-2-alpha transcription factor network | |||||
3 | S1P3 pathway | |||||
4 | VEGF and VEGFR signaling network | |||||
5 | VEGFR1 specific signals | |||||
6 | Signaling events mediated by VEGFR1 and VEGFR2 | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | Neurophilin interactions with VEGF and VEGFR | |||||
2 | VEGF binds to VEGFR leading to receptor dimerization | |||||
WikiPathways | [+] 3 WikiPathways | + | ||||
1 | Focal Adhesion | |||||
2 | Signaling by VEGF | |||||
3 | Angiogenesis |
Target-Related Models and Studies | Top | |||||
---|---|---|---|---|---|---|
Target Validation |
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23. | |||||
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: 6974). | |||||
REF 3 | 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6. | |||||
REF 4 | 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: 5705). | |||||
REF 5 | ClinicalTrials.gov (NCT00348790) Vatalanib in Treating Patients With Recurrent or Progressive Meningioma. U.S. National Institutes of Health. | |||||
REF 6 | MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33. | |||||
REF 7 | 2011 Pipeline of Sirna Therapeutics. | |||||
REF 8 | Inhibitors of VEGF receptors-1 and -2 based on the 2-((pyridin-4-yl)ethyl)pyridine template. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1913-9. | |||||
REF 9 | Future pharmacological treatment options for nonexudative and exudative age-related macular degeneration. Expert Opin Emerg Drugs. 2005 Feb;10(1):119-35. | |||||
REF 10 | 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 11 | 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 12 | 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 13 | Synthesis and biological activity of N(4)-phenylsubstituted-6-(2,4-dichloro phenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as vascular endo... Bioorg Med Chem. 2010 May 15;18(10):3575-87. | |||||
REF 14 | 1-Acyl-1H-[1,2,4]triazole-3,5-diamine analogues as novel and potent anticancer cyclin-dependent kinase inhibitors: synthesis and evaluation of biological activities. J Med Chem. 2005 Jun 30;48(13):4208-11. | |||||
REF 15 | Rational design, structure, and biological evaluation of cyclic peptides mimicking the vascular endothelial growth factor. J Med Chem. 2007 Oct 18;50(21):5135-46. | |||||
REF 16 | Biochemical and structural analysis of the binding determinants of a vascular endothelial growth factor receptor peptidic antagonist. J Med Chem. 2010 Jun 10;53(11):4428-40. | |||||
REF 17 | New cytotoxic bisindole alkaloids with protein tyrosine kinase inhibitory activity from a myxomycete Lycogala epidendrum. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2776-80. | |||||
REF 18 | On-resin cyclization of peptide ligands of the Vascular Endothelial Growth Factor Receptor 1 by copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloa... Bioorg Med Chem Lett. 2007 Oct 15;17(20):5590-4. | |||||
REF 19 | Macrocyclic ureas as potent and selective Chk1 inhibitors: an improved synthesis, kinome profiling, structure-activity relationships, and prelimina... Bioorg Med Chem Lett. 2007 Dec 1;17(23):6593-601. | |||||
REF 20 | The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.