| + |
SRC | up-regulates 
phosphorylation
|
FLT4 |
0.491 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165035 |
Tyr1063 |
FGLARDIyKDPDYVR |
Homo sapiens |
|
| pmid |
sentence |
| 20431062 |
Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337 vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165039 |
Tyr1333 |
ARGGQVFyNSEYGEL |
Homo sapiens |
|
| pmid |
sentence |
| 20431062 |
Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337, demonstrating that integrin-mediated receptor phosphorylation induces a phosphorylation pattern that is distinct from that induced by growth factors. Furthermore, pull-down assays show that integrin-mediated vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165043 |
Tyr1337 |
QVFYNSEyGELSEPS |
Homo sapiens |
|
| pmid |
sentence |
| 20431062 |
Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337, demonstrating that integrin-mediated receptor phosphorylation induces a phosphorylation pattern that is distinct from that induced by growth factors. Furthermore, pull-down assays show that integrin-mediated vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165047 |
Tyr830 |
PLEEQCEyLSYDASQ |
Homo sapiens |
|
| pmid |
sentence |
| 20431062 |
Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337 vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165051 |
Tyr833 |
EQCEYLSyDASQWEF |
Homo sapiens |
|
| pmid |
sentence |
| 20431062 |
Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337, demonstrating that integrin-mediated receptor phosphorylation induces a phosphorylation pattern that is distinct from that induced by growth factors. Furthermore, pull-down assays show that integrin-mediated vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-165055 |
Tyr853 |
HLGRVLGyGAFGKVV |
Homo sapiens |
|
| pmid |
sentence |
| 20431062 |
Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337 vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk. |
|
| Publications: |
6 |
Organism: |
Homo Sapiens |
| + |
FLT4 | up-regulates activity
phosphorylation
|
FLT4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104072 |
Tyr1230 |
RHSLAARyYNWVSFP |
Homo sapiens |
Aorta Endothelium |
| pmid |
sentence |
| 12881528 |
Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104076 |
Tyr1231 |
HSLAARYyNWVSFPG |
Homo sapiens |
|
| pmid |
sentence |
| 12881528 |
Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104080 |
Tyr1265 |
FPMTPTTyKGSVDNQ |
Homo sapiens |
Aorta Endothelium |
| pmid |
sentence |
| 12881528 |
Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104084 |
Tyr1333 |
ARGGQVFyNSEYGEL |
Homo sapiens |
Aorta Endothelium |
| pmid |
sentence |
| 12881528 |
Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104088 |
Tyr1337 |
QVFYNSEyGELSEPS |
Homo sapiens |
Aorta Endothelium |
| pmid |
sentence |
| 12881528 |
Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-104092 |
Tyr1363 |
TFFTDNSy |
Homo sapiens |
Aorta Endothelium |
| pmid |
sentence |
| 12881528 |
Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail. |
|
| Publications: |
6 |
Organism: |
Homo Sapiens |
| + |
FLT4 | up-regulates activity
phosphorylation
|
GLO1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-276180 |
Tyr136 |
GIAVPDVySACKRFE |
in vitro |
|
| pmid |
sentence |
| 34838714 |
We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
FLT4 |
phosphorylation
|
SHC1 |
0.574 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64186 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
|
| pmid |
sentence |
| 9927207 |
We have investigated which of the shc tyrosine residues are targeted by the vegfr3/ flt4 kinase and the role of the shc ptb and sh2 domains in this process. Our results show that y239/ y240 and y313 are simultaneously phosphorylated by the kinase, creating grb2 binding sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64076 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
|
| pmid |
sentence |
| 9927207 |
We have investigated which of the shc tyrosine residues are targeted by the vegfr3/ flt4 kinase and the role of the shc ptb and sh2 domains in this process. Our results show that y239/ y240 and y313 are simultaneously phosphorylated by the kinase, creating grb2 binding sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-64190 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
|
| pmid |
sentence |
| 9927207 |
We have investigated which of the shc tyrosine residues are targeted by the vegfr3/ flt4 kinase and the role of the shc ptb and sh2 domains in this process. Our results show that y239/ y240 and y313 are simultaneously phosphorylated by the kinase, creating grb2 binding sites. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
FLT4 | down-regulates 
phosphorylation
|
RPS6KA3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-98708 |
Tyr707 |
KGAMAATySALNRNQ |
Homo sapiens |
|
| pmid |
sentence |
| 12601080 |
Upon truncation of this c-terminal stretch, or mutation of the tyr-707 residue alone, autoinhibition is attenuated, and the kinase becomes constitutively active. Based on these findings we propose that phosphorylation of the tyr-707 represents a novel alternative regulatory mechanism for p90rsk activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
regorafenib | down-regulates activity
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259206 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24756792 |
In biochemical in vitro or cell-based assays, Regorafenib or its major human active metabolites M-2 and M-5 inhibited the activity of RET,VEGFR 1-3, KIT, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, TrkA, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl at concentrations that can be achieved clinically. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
sorafenib tosylate | down-regulates activity
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259224 |
|
|
in vitro |
|
| pmid |
sentence |
| 16757355 |
Further characterization of sorafenib revealed that this molecule was a multikinase inhibitor that targeted the vascular endothelial growth factor receptor family (VEGFR-2 and VEGFR-3) and platelet-derived growth factor receptor family (PDGFR-beta and Kit), which play key roles in tumor progression and angiogenesis. The in vitro and cellular profile of sorafenib is summarized in Table I. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
sunitinib | down-regulates activity
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257848 |
|
|
Homo sapiens |
MV4-11 Cell |
| pmid |
sentence |
| 20570526 |
Sunitinib [inhibits KDR, PDGFR2, PDGFRβ, c-KIT and FLT3; approved for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors], |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
sunitinib | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-163944 |
|
|
Homo sapiens |
B-lymphocyte |
| pmid |
sentence |
| 20185585 |
The vegfr/pdgfr inhibitor sunitinib (selleck) was used at 35 mg/kg in citrate-buffered water and administered daily by oral gavage for 7 days. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-176754 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21993628 |
The vegfr/pdgfr inhibitor sunitinib (selleck) was used at 35 mg/kg in citrate-buffered water and administered daily by oral gavage for 7 days. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
N-[[3-fluoro-4-[[2-(1-methyl-4-imidazolyl)-7-thieno[3,2-b]pyridinyl]oxy]anilino]-sulfanylidenemethyl]-2-phenylacetamide | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-194337 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
pazopanib | down-regulates activity
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258261 |
|
|
in vitro |
|
| pmid |
sentence |
| 22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257739 |
|
|
Homo sapiens |
HUVEC Cell |
| pmid |
sentence |
| 18620382 |
Pyrimidine 13 showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine receptor kinases PDGFRβ, c-Kit, FGF-R1, and c-fms with IC50’s of 84, 74, 140, and 146 nM, respectively. |
|
| Publications: |
2 |
Organism: |
In Vitro, Homo Sapiens |
| + |
VEGFC | up-regulates
binding
|
FLT4 |
0.934 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-55205 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9435229 |
Vegf-c, was isolated as a ligand for the tyrosine kinase vegfr-3 (flt4) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle, Skeletal Muscle, Lung |
| + |
lenvatinib | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-191454 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
pazopanib hydrochloride | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-200809 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
nintedanib | down-regulates activity
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257801 |
|
|
in vitro |
|
| pmid |
sentence |
| 18559524 |
In this report, we describe the preclinical profile of BIBF 1120, a combined VEGFR, FGFR, and PDGFR inhibitor currently entering phase III clinical studies in non–small cell lung carcinoma and other cancers. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
VEGFD | up-regulates
binding
|
FLT4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-55065 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9435229 |
Vegf-d is a ligand for both vegf receptors (vegfrs) vegfr-2 (flk1) and vegfr-3 (flt4) and can activate these receptors. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
linifanib | down-regulates activity
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262207 |
|
|
in vitro |
|
| pmid |
sentence |
| 16648571 |
ABT-869 is a structurally novel, receptor tyrosine kinase (RTK) inhibitor that is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor families |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
1-[2-chloro-4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl]-3-(5-methyl-3-isoxazolyl)urea | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-207299 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KRN-633 | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-193585 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
motesanib | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-194563 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Telatinib | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-207221 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
nintedanib | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-190302 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
axitinib | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-171860 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 21297102 |
Axitinib , a highly selective inhibitor of vascular endothelial growth factor receptors taken orally, is approved for second-line treatment of advanced renal cell carcinoma (rcc) after failure of prior treatment with sunitinib or a cytokine. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TBX1 | up-regulates quantity by expression 
transcriptional regulation
|
FLT4 |
0.313 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251869 |
|
|
Homo sapiens |
Endothelial Cell |
| pmid |
sentence |
| 20439995 |
Tbx1 plays a critical role in lymphatic vessel development and regulates the expression of Vegfr3, a gene that is essential for lymphangiogenesis. Tbx1 activates Vegfr3 transcription in endothelial cells (ECs) by binding to an enhancer element in the Vegfr3 gene. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
motesanib | down-regulates activity
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258252 |
|
|
in vitro |
|
| pmid |
sentence |
| 22037378 |
Our data set represents the most detailed comprehensive assessment of the reactivity of known and clinical kinase inhibitors across the kinome published to date. | The data also show that for at least 15 of the 27 kinases that are the primary, intended targets for the compounds tested and that are represented in the assay panel, selective inhibitors, as assessed by both absolute selectivity across the kinome and selectivity relative to the primary target, are among the 72 tested here. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
Brivanib alaninate | down-regulates
chemical inhibition
|
FLT4 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-190729 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
FLT4
- 
- 