| + |
FLT3 | down-regulates activity 
phosphorylation
|
IDH2 |
0.432 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267632 |
Tyr107 |
SALATQKySVAVKCA |
Homo sapiens |
Acute Myeloid Leukemia Cell |
| pmid |
sentence |
| 34289383 |
FLT3 promotes mIDH2 acetylation through Y107 phosphorylation of mIDH2 that enhances ACAT1 recruitment, |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, NPM1_new |
| + |
FLT3 | down-regulates activity
phosphorylation
|
SIRT3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267631 |
Tyr226 |
KGLLLRLyTQNIDGL |
in vitro |
|
| pmid |
sentence |
| 34289383 |
We also hypothesize that, besides activating ACAT1 through Y407 phosphorylation (Fan et al., 2016), FLT3 might simultaneously phosphorylate and regulate SIRT3. Our mutational studies on all of the seven tyrosine sites of SIRT3 revealed that purified rFLT3 directly phosphorylated purified rSIRT3 in an in vitro kinase assay, leading to decreased SIRT3 deacetylase activity that was assessed by ability to deacetylate K413 of mIDH2 (Figure 4H, first three samples in left, middle, and right panels), whereas replacement of Y226 completely abolished inhibition of SIRT3 by FLT3 (Figure 4H, right). |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
FLT3 | up-regulates activity 
phosphorylation
|
SHC1 |
0.436 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251146 |
Tyr349 |
EEPPDHQyYNDFPGK |
Homo sapiens |
|
| pmid |
sentence |
| 10482988 |
Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251147 |
Tyr350 |
EPPDHQYyNDFPGKE |
Homo sapiens |
|
| pmid |
sentence |
| 10482988 |
Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251148 |
Tyr427 |
ELFDDPSyVNVQNLD |
Homo sapiens |
|
| pmid |
sentence |
| 10482988 |
Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261540 |
|
|
Mus musculus |
32D Cell |
| pmid |
sentence |
| 15769897 |
we observed constitutive activation of Erk-1 and Erk-2, Akt, and of Shc by both Flt3-ITD and Flt3-D835Y |
|
| Publications: |
4 |
Organism: |
Homo Sapiens, Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, miRNA in AML, FLT3-ITD in AML |
| + |
FLT3 | up-regulates activity
phosphorylation
|
IDH1 |
0.435 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267630 |
Tyr391 |
PNVQRSDyLNTFEFM |
in vitro |
|
| pmid |
sentence |
| 34289383 |
Moreover, in an in vitro kinase assay, purified recombinant FLT3 (rFLT3) phosphorylated recombinant IDH2 R140Q mutant but did not alter its catalytic activity (Figure 1C), whereas rFLT3 phosphorylated mIDH1 protein and enhanced its catalytic activity |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267629 |
Tyr42 |
VELDLHSyDLGIENR |
in vitro |
|
| pmid |
sentence |
| 34289383 |
Moreover, in an in vitro kinase assay, purified recombinant FLT3 (rFLT3) phosphorylated recombinant IDH2 R140Q mutant but did not alter its catalytic activity (Figure 1C), whereas rFLT3 phosphorylated mIDH1 protein and enhanced its catalytic activity |
|
| Publications: |
2 |
Organism: |
In Vitro |
| Pathways: | Acute Myeloid Leukemia, NPM1_new |
| + |
FLT3 | up-regulates activity
phosphorylation
|
ACAT1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267628 |
Tyr407 |
HALKQGEyGLASICN |
Homo sapiens |
Acute Myeloid Leukemia Cell |
| pmid |
sentence |
| 34289383 |
We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3 | up-regulates
phosphorylation
|
FLT3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-117571 |
Tyr589 |
TGSSDNEyFYVDFRE |
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 11971190 |
Previously we reported that flt3 with itd (flt3/itd) formed a homodimer and was autophosphorylated on tyrosine residuewe examined the role of tyr residues (y589, y591, y597 and y599) in the jm domain in the activation of flt3. In wt-flt3, these tyr residues were important for the fl-dependent activation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-117575 |
Tyr591 |
SSDNEYFyVDFREYE |
Homo sapiens |
|
| pmid |
sentence |
| 11971190 |
Previously we reported that flt3 with itd (flt3/itd) formed a homodimer and was autophosphorylated on tyrosine residuewe examined the role of tyr residues (y589, y591, y597 and y599) in the jm domain in the activation of flt3. In wt-flt3, these tyr residues were important for the fl-dependent activation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-117579 |
Tyr597 |
FYVDFREyEYDLKWE |
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 11971190 |
Previously we reported that flt3 with itd (flt3/itd) formed a homodimer and was autophosphorylated on tyrosine residuewe examined the role of tyr residues (y589, y591, y597 and y599) in the jm domain in the activation of flt3. In wt-flt3, these tyr residues were important for the fl-dependent activation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-117583 |
Tyr599 |
VDFREYEyDLKWEFP |
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 11971190 |
Previously we reported that flt3 with itd (flt3/itd) formed a homodimer and was autophosphorylated on tyrosine residuewe examined the role of tyr residues (y589, y591, y597 and y599) in the jm domain in the activation of flt3. In wt-flt3, these tyr residues were important for the fl-dependent activation |
|
| Publications: |
4 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, ASXL1 in AML, FLT3 in AML, miRNA in AML, AML_TRIPLETS, FLT3-ITD in AML, FLT3-ITD signaling, Triple mutant AML, NPM1_new, WNT/FLT3 |
| + |
FLT3 | up-regulates activity
phosphorylation
|
FLT3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271926 |
Tyr589 |
TGSSDNEyFYVDFRE |
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 16627759 |
In vitro mapping of FLT3 autophosphorylation sites|Tryptic peptides covering more than 80% of the FLT3 kinase domain were recovered, and 5 tyrosine residues (Y591, Y726, Y842, Y955, and Y969) within this region were phosphorylated.|This finding suggests that the combination of tyrosine residues 589 and 591 is required for activation of STAT-5 signaling pathways. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271921 |
Tyr591 |
SSDNEYFyVDFREYE |
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 16627759 |
In vitro mapping of FLT3 autophosphorylation sites|Tryptic peptides covering more than 80% of the FLT3 kinase domain were recovered, and 5 tyrosine residues (Y591, Y726, Y842, Y955, and Y969) within this region were phosphorylated.|This finding suggests that the combination of tyrosine residues 589 and 591 is required for activation of STAT-5 signaling pathways. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271925 |
Tyr842 |
DIMSDSNyVVRGNAR |
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 16627759 |
In vitro mapping of FLT3 autophosphorylation sites|Tryptic peptides covering more than 80% of the FLT3 kinase domain were recovered, and 5 tyrosine residues (Y591, Y726, Y842, Y955, and Y969) within this region were phosphorylated. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271919 |
Tyr969 |
VSECPHTyQNRRPFS |
Homo sapiens |
|
| pmid |
sentence |
| 31395582 |
A mutation at tyrosine 969, which inhibits activation of downstream signaling by FLT3-ITD. |
|
| Publications: |
4 |
Organism: |
Mus Musculus, Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, ASXL1 in AML, FLT3 in AML, miRNA in AML, AML_TRIPLETS, FLT3-ITD in AML, FLT3-ITD signaling, Triple mutant AML, NPM1_new, WNT/FLT3 |
| + |
PIM1 | up-regulates quantity
phosphorylation
|
FLT3 |
0.43 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259927 |
Tyr591 |
SSDNEYFyVDFREYE |
Homo sapiens |
MOLM-14 Cell |
| pmid |
sentence |
| 24040307 |
Pim-1 Kinase Phosphorylates and Stabilizes 130 kDa FLT3 and Promotes Aberrant STAT5 Signaling in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication[...]Pim-1 inhibition also decreased phosphorylation of FLT3 at tyrosine 591 and of STAT5, and expression of Pim-1 itself, consistent with inhibition of the FLT3-ITD-STAT5 signaling pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, FLT3-ITD in AML, FLT3-ITD signaling |
| + |
FLT3 | up-regulates activity
phosphorylation
|
STAT5A |
0.597 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245069 |
Tyr694 |
LAKAVDGyVKPQIKQ |
Mus musculus |
32D Cell |
| pmid |
sentence |
| 17356133 |
in vitro kinase assays revealed that STAT5 is a direct target of Flt3 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261516 |
|
|
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 12796379 |
FLT3-ITDs induced a strong activation of STAT5. FLT3-ITD mutants induce an autophosphorylation of the receptor, interleukin 3-independent growth in Ba/F3 cells, and a strong STAT5 and mitogen-activated protein kinase (MAPK) activation. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, FLT3 in AML, miRNA in AML, AML_TRIPLETS, FLT3-ITD in AML, FLT3-ITD signaling, Triple mutant AML |
| + |
FLT3 |
phosphorylation
|
FLT3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271922 |
Tyr726 |
KEHNFSFyPTFQSHP |
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 16627759 |
In vitro mapping of FLT3 autophosphorylation sites|Tryptic peptides covering more than 80% of the FLT3 kinase domain were recovered, and 5 tyrosine residues (Y591, Y726, Y842, Y955, and Y969) within this region were phosphorylated. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271924 |
Tyr842 |
DIMSDSNyVVRGNAR |
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 28271164 |
Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD|Phosphorylation on several critical tyrosine residues is known to be essential for FLT3 signaling. Among these tyrosine residues, Y842 is located in the so-called activation loop. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271923 |
Tyr955 |
ADAEEAMyQNVDGRV |
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 16627759 |
In vitro mapping of FLT3 autophosphorylation sites|Tryptic peptides covering more than 80% of the FLT3 kinase domain were recovered, and 5 tyrosine residues (Y591, Y726, Y842, Y955, and Y969) within this region were phosphorylated. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271920 |
Tyr969 |
VSECPHTyQNRRPFS |
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 16627759 |
In vitro mapping of FLT3 autophosphorylation sites|Tryptic peptides covering more than 80% of the FLT3 kinase domain were recovered, and 5 tyrosine residues (Y591, Y726, Y842, Y955, and Y969) within this region were phosphorylated. |
|
| Publications: |
4 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, ASXL1 in AML, FLT3 in AML, miRNA in AML, AML_TRIPLETS, FLT3-ITD in AML, FLT3-ITD signaling, Triple mutant AML, NPM1_new, WNT/FLT3 |
| + |
SYK | up-regulates activity
phosphorylation
|
FLT3 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278431 |
Tyr768 |
HSEDEIEyENQKRLE |
Homo sapiens |
|
| pmid |
sentence |
| 24525236 |
Only two mutants, FLT3-KD (V5) Y768A and Y955A, were resistant to SYK-mediated FLT3 phosphorylation, suggesting that SYK directly phosphorylates FLT3 at sites Y768 and Y955 ( ).|SYK Enhances FLT3 WT and Mutant Activation by Phosphorylation of Residues Y768 and Y955. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278430 |
Tyr955 |
ADAEEAMyQNVDGRV |
Homo sapiens |
|
| pmid |
sentence |
| 24525236 |
Only two mutants, FLT3-KD (V5) Y768A and Y955A, were resistant to SYK mediated FLT3 phosphorylation, suggesting that SYK directly phosphorylates FLT3 at sites Y768 and Y955 (XREF_FIG).|SYK Enhances FLT3 WT and Mutant Activation by Phosphorylation of Residues Y768 and Y955. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
FLT3 | down-regulates activity
phosphorylation
|
CDKN1B |
0.294 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269208 |
Tyr88 |
KGSLPEFyYRPPRPP |
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 28522571 |
FLT3 and FLT3-ITD phosphorylate and inactivate the cyclin-dependent kinase inhibitor p27 Kip1 in acute myeloid leukemia|P27Kip1 (p27) can prevent cell proliferation by inactivating cyclin-dependent kinases. This function is impaired upon phosphorylation of p27 at tyrosine residue 88. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia |
| + |
FLT3 | up-regulates quantity by expression 
transcriptional regulation
|
USP22 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261559 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26049753 |
USP22 deubiquitinase was overexpressed in FLT3-ITD positive AML CD34+ cells.USP22 expression was regulated by c-MYC and contributed to c-MYC mediated reduction in SIRT1 polyubiquitination and degradation. USP22 directly interacted with and removing polyubiquitin chains from SIRT1 to increase SIRT1 protein stabilization and expression. These results support a role for USP22 in MYC-mediated increase in SIRT1 protein stabilization, and indicate that FLT3-ITD, c-MYC and USP22 form an oncogenic network that enhances SIRT1 expression and activity in leukemic cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
FLT3 | up-regulates activity
|
AKT1 |
0.442 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252626 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16266983 |
We show that the presence of Flt3-ITD constitutively activates Akt (PKB), a key serine-threonine kinase within the phosphatidylinositol 3-kinase pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
JNJ-28312141 free base | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258125 |
|
|
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-259749 |
|
|
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: |
2 |
Organism: |
In Vitro |
| + |
FLT3 | down-regulates quantity by repression 
transcriptional regulation
|
CEBPA |
0.625 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249635 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16146838 |
Oncogenic mutations of Flt3 also result in the activation of aberrant signaling pathways, including strong activation of STAT5, induction of STAT target genes, and repression of myeloid transcription factors c/EBP-3 and Pu.1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261529 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14592841 |
Thus, induction of C/EBPα and PU.1 expression is inhibited in 32D cells due to the expression of FLT3/ITD |
|
| Publications: |
2 |
Organism: |
Homo Sapiens, Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, FLT3 in AML, AML_TRIPLETS, FLT3-ITD in AML, Triple mutant AML, NPM1_new |
| + |
FLT3 | down-regulates quantity by repression
transcriptional regulation
|
SPI1 |
0.614 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249634 |
|
|
|
|
| pmid |
sentence |
| 16146838 |
Oncogenic mutations of Flt3 also result in the activation of aberrant signaling pathways, including strong activation of STAT5, induction of STAT target genes, and repression of myeloid transcription factors c/EBP-3 and Pu.1. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261530 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14592841 |
This data confirms that PU.1 is a downstream target of activated C/EBPα and is suppressed in FLT3/ITD-expressing cells as a result of C/EBPα suppression. |
|
| Publications: |
2 |
Organism: |
, Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, miRNA in AML, FLT3-ITD in AML |
| + |
Ast-487 | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259693 |
|
|
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-258173 |
|
|
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: |
2 |
Organism: |
In Vitro |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
SOCS2 |
0.437 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261545 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 12468433 |
We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
FLT3 | up-regulates quantity by stabilization
post transcriptional regulation
|
SIRT1 |
0.357 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261555 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26049753 |
SIRT1 protein but not mRNA expression is increased in CD34+ cells from FLT3-ITD positive AML patients compared to FLT3 wild-type AML patients |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
PIM2 |
0.343 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261541 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 15769897 |
The serine-threonine kinase Pim-2 is a functionally relevant downstream target of STAT5.24 Here, we observed only a weak induction of Pim-2 by Flt3-D835Y compared to the effects of Flt3-ITD. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
FLT3 | up-regulates activity
|
RUNX1 |
0.369 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256307 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28213513 |
Our finding that RUNX1 protein levels are dependent on FLT3-ITD signaling in AML cells and that, together, they synergize to generate AML. […]Our work demonstrated that Tyr phosphorylation within the ID region of RUNX1 is critical for its oncogenic potential, |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, miRNA in AML, NPM1_new |
| + |
sunitinib | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-172911 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21423276 |
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-163941 |
|
|
Homo sapiens |
|
| 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-176751 |
|
|
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: |
3 |
Organism: |
Homo Sapiens |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
SOCS3 |
0.285 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261546 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 12468433 |
We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
anthra[1,9-cd]pyrazol-6(2H)-one | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-170614 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21159646 |
In comparison, in the same assay conditions, the previously reported mps1 inhibitor sp600125 (13) was 10-fold less potent than nms-p715 on mps1 and, in addition, it was highly unspecific, being more active on at least 12 kinases including mitotic kinases with ic50 values well below 1 ?mol/l |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3 | up-regulates activity
|
RAC1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261536 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 18192505 |
Inhibition of FLT3/ITD leads to a small decrease in RAC1 activity |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML, WNT/FLT3 |
| + |
TG101209 | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-207260 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3LG | up-regulates
binding
|
FLT3 |
0.882 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-65564 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10080542 |
Flt3 ligand (fl) is an early-acting potent co-stimulatory cytokine that regulates proliferation and differentiation of a number of blood cell lineages. Its receptor flt3/flk2 belongs to class iii receptor tyrosine kinases that also include the receptors for colony-stimulating factor 1 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-99750 |
|
|
Homo sapiens |
Leukemia Cell |
| pmid |
sentence |
| 12681969 |
Flt3 is activated by binding of its natural flt3-ligand (flt3-l), |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, FLT3-ITD in AML |
| + |
dovitinib; bis(lactic acid) | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-191418 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
sunitinib | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258290 |
|
|
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-257849 |
|
|
Homo sapiens |
|
| 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: |
2 |
Organism: |
In Vitro, Homo Sapiens |
| + |
FLT3 | down-regulates quantity by repression
transcriptional regulation
|
CDKN1B |
0.294 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261524 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14981546 |
FLT3-ITD signaling contributes to transcriptional inhibition of p27Kip1 and Bim gene expression |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia |
| + |
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)-4-pyrimidinyl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258294 |
|
|
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 |
| + |
FLT3 | up-regulates activity
binding
|
GRB10 |
0.369 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255947 |
|
|
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 23246379 |
These results suggest that Grb10 binds to both normal and oncogenic FLT3 and induces PI3K–Akt and STAT5 signaling pathways resulting in an enhanced proliferation, survival and colony formation of hematopoietic cells. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, FLT3-ITD signaling |
| + |
4-amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydrobenzimidazol-2-ylidene]-2-quinolinone | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-191406 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
midostaurin | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258247 |
|
|
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-256308 |
|
|
in vitro |
|
| pmid |
sentence |
| 12124173 |
PKC412 is a potent inhibitor of mutant FLT3 and is a candidate for testing as an antileukemia agent in AML patients with mutant FLT3 receptors. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
| + |
FLT3 | down-regulates activity
|
PTPRJ |
0.501 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261553 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 22438257 |
Taken together, the described findings supported the notion that FLT3 ITD causes reduced DEP-1 activity compared with cells expressing WT FLT3 rather than alterations in mRNA or protein levels. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
FLT3 | up-regulates activity
phosphorylation
|
CTNNB1 |
0.419 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260124 |
|
|
Homo sapiens |
Acute Myeloid Leukemia Cell |
| pmid |
sentence |
| 17851558 |
Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, FLT3 in AML, FLT3-ITD in AML, FLT3-ITD signaling, WNT/FLT3 |
| + |
regorafenib | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259214 |
|
|
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 |
| + |
MK-2461 | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-194378 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
XRCC5 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261684 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 21228325 |
We detected an approximately 5-fold decrease in Ku86 expression in early pro-B cells from FLT3/ITD mice compared with the wild-type controls. These data support the finding that FLT3/ITD mutations exert a suppressive role on Ku86 expression. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
FLT3 | up-regulates activity
|
ERK1/2 |
0.296 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261521 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14981546 |
These data confirm previous findings that FLT3 receptors with ITD mutations efficiently trigger the activation of ERK, STAT5 and Akt in the absence of FL stimulation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260132 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30552988 |
Oncogenic, constitutively active mutants of FLT3 are known to be expressed in acute myeloid leukemia and to correlate with poor prognosis. Activation of the receptor mediates cell survival, cell proliferation and differentiation of cells. Several of the signal transduction pathways downstream of FLT3 have been shown to include various members of the SRC family of kinases (SFKs). They are involved in regulating the activity of RAS/ERK pathways through the scaffolding protein GAB2 and the adaptor protein SHC. |
|
| Publications: |
2 |
Organism: |
Mus Musculus, Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, AML_TRIPLETS, FLT3-ITD in AML, FLT3-ITD signaling, Triple mutant AML, NPM1_new, WNT/FLT3 |
| + |
FLT3 | up-regulates activity
phosphorylation
|
AKT |
0.442 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261522 |
|
|
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 14981546 |
These data confirm previous findings that FLT3 receptors with ITD mutations efficiently trigger the activation of ERK, STAT5 and Akt in the absence of FL stimulation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, ASXL1 in AML, FLT3 in AML, miRNA in AML, AML_TRIPLETS, FLT3-ITD in AML, FLT3-ITD signaling, Triple mutant AML, NPM1_new, WNT/FLT3 |
| + |
FLT3 | up-regulates activity
|
AKT |
0.442 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245064 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16266983 |
We show that the presence of Flt3-ITD constitutively activates Akt (PKB), a key serine-threonine kinase within the phosphatidylinositol 3-kinase pathway. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, ASXL1 in AML, FLT3 in AML, miRNA in AML, AML_TRIPLETS, FLT3-ITD in AML, FLT3-ITD signaling, Triple mutant AML, NPM1_new, WNT/FLT3 |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
PARP1 |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261554 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 21228325 |
Interestingly, quantitative RT-PCR analysis demonstrated a 2-fold increase in PARP-1 expression. Western blotting analysis of protein nuclear extracts from FLT3/ITD B-cells confirmed that PARP1 was up-regulated, compared with wild-type controls |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML, FLT3-ITD signaling |
| + |
tandutinib | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-207209 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
tandutinib | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258296 |
|
|
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 |
| + |
quizartinib | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-206331 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | FLT3-ITD signaling |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
RAD51 |
0.254 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261550 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 15626738 |
FLT3-ITD-TKD dual mutants induce hyperactivation of STAT5 and up-regulation of its downstream targets Bcl-x(L) and RAD51 in Ba/F3 cells |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML, FLT3-ITD signaling |
| + |
FLT3 | down-regulates activity
|
FOXO3 |
0.314 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261523 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14981546 |
Immunoblot analysis indicated an increased level of Foxo3a phosphorylation on residue Thr32, as shown by the appearance of additional slower-migrating phospho-species immediately after induction of FLT3-ITD4 expression |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | FLT3 in AML |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
FZD4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260121 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 15650056 |
Microarray analyses revealed higher mRNA expression of Frizzled-4, a receptor for Wnt ligands in 32D/Flt3-ITD cells. Findings were verified by quantitative realtime reverse transcription–polymerase chain reaction (RT-PCR) and on the protein level. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261533 |
|
|
Mus musculus |
32D Cell |
| pmid |
sentence |
| 15650056 |
AML-typical Flt3 mutations induce the expression of Frizzled-4 on the mRNA and protein level, mimicking the effects of IL-3. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
CDKN1A |
0.292 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261520 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 15003515 |
Flt3 Mutation Activates p21WAF1/CIP1 Gene Expression Through the Action of STAT5. Through the Action of STAT5. Co-transfection of p21 promoter-luciferase constructs with Flt3-ITD plasmid into K562 and BaF3 cells results in the induction of p21 promoter activity and a -692/-684 STAT site is important for the induction. STAT5a binds specifically to this element and Flt3-ITD enhances the protein binding to this site. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML, FLT3-ITD signaling |
| + |
FLT3 | down-regulates quantity by repression
transcriptional regulation
|
PTPN6 |
0.372 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261532 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15574429 |
Expression of FLT3/ITD induces down-regulation of SHP-1 expression and activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, FLT3-ITD in AML |
| + |
FLT3 | down-regulates activity
relocalization
|
NCOR2 |
0.26 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261538 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14982881 |
We report here that the Flt3-ITD interferes with the transcriptional and biologic action of the PLZF transcriptional repressor. In the presence of Flt3-ITD, PLZF-SMRT interaction was reduced, transcriptional repression by PLZF was inhibited, and PLZF-mediated growth suppression of leukemia cells was partially blocked. Furthermore, overexpression of Flt3-ITD led to a partial relocalization of SMRT protein from the nucleus to the cytoplasm. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
[4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-(1-piperazinyl)methanone | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-193615 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
ID1 |
0.266 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255698 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 18559972 |
In this study, we used specific tyrosine kinase inhibitors to identify critical target genes that are regulated by oncogenic tyrosine kinases. Using oligonucleotide microarrays, we identified genes that are either up- or down-regulated by selective small molecule inhibitors that target the ABL, PDGFβR, or FLT3 kinases. Genes induced by these inhibitors are presumably repressed by activated tyrosine kinases.Among these genes, we detected a 5- to 50-fold reduction in Id1 expression when the cancer cells were treated with inhibitors. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, miRNA in AML |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
CISH |
0.303 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261542 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 15769897 |
The STAT5 target gene CIS, a member of the suppressor of cytokine signaling (SOCS) protein family, was highly induced by Flt3-ITD |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
PTPRJ | down-regulates activity
dephosphorylation
|
FLT3 |
0.501 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277092 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21262971 |
Moreover, activated FLT3 could be dephosphorylated by recombinant DEP-1 in vitro.|The data indicate that DEP-1 is negatively regulating FLT3 signaling activity and that its loss may contribute to but is not sufficient for leukemogenic cell transformation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
PIM1 |
0.43 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261519 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 15498859 |
Pim-1 is a proto-oncogene and is known to be up-regulated by signal transducer and activator of transcription 5 (STAT5), which itself is a downstream target of FLT3 signaling. constitutively activated FLT3 signaling up-regulates Pim-1 expression in leukemia cells. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, FLT3-ITD in AML, FLT3-ITD signaling |
| + |
4-amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydrobenzimidazol-2-ylidene]-2-quinolinone | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258210 |
|
|
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 |
| + |
FLT3 | up-regulates activity
|
Hexokinase |
0.267 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-270268 |
|
|
Homo sapiens |
Acute Lymphoblastic Leukemia Cell Line |
| pmid |
sentence |
| 28194038 |
FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3 | up-regulates
|
Skeletal_muscle_differentiation |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-202105 |
|
|
Homo sapiens |
Myoblast, Myofibroblast |
| pmid |
sentence |
| 23704355 |
Here we report the identification of flt3l (fms-like tyrokine kinase 3 ligand) signaling as a novel regulator of skeletal myogenesis |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Muscle, Skeletal Muscle |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
BCL2L1 |
0.343 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261549 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 15626738 |
FLT3-ITD-TKD dual mutants induce hyperactivation of STAT5 and up-regulation of its downstream targets Bcl-x(L) and RAD51 in Ba/F3 cells |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
CBL | down-regulates activity
binding
|
FLT3 |
0.445 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255739 |
|
|
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 19276253 |
Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
| + |
CBLB | down-regulates activity
ubiquitination
|
FLT3 |
0.33 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260106 |
|
|
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 19276253 |
Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
| + |
FLT3 | up-regulates activity
binding
|
GRB2 |
0.593 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245060 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 10080542 |
FL stimulation induces association of Grb2 with Flt3, SHP-2,and Shc |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML |
| + |
ponatinib | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261983 |
|
|
in vitro |
|
| pmid |
sentence |
| 23430109 |
We assessed the in vitro activity of ponatinib against clinically relevant FLT3-ITD mutant isoforms that confer resistance to AC220 or sorafenib. Substitution of the FLT3 "gatekeeper" phenylalanine with leucine (F691L) conferred mild resistance to ponatinib, but substitutions at the FLT3 activation loop (AL) residue D835 conferred a high degree of resistance. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
FLT3 | up-regulates activity
binding
|
PTPN11 |
0.538 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-245057 |
|
|
Mus musculus |
32D Cell |
| pmid |
sentence |
| 16684964 |
Y599 was additionally found to interact with the protein tyrosine phosphatase SHP2 in a phosphorylation-dependent manner. As Y599F-Flt3-32D was unable to associate with and to phosphorylate SHP2 and since silencing of SHP2 in WT-Flt3-expressing cells mimicked the Y599F-Flt3 phenotype, we hypothesize that recruitment of SHP2 to pY599 contributes to FL-mediated Erk activation and proliferation. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, AML_TRIPLETS, FLT3-ITD signaling, NPM1_new |
| + |
FLT3 | down-regulates activity
|
ZBTB16 |
0.319 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261537 |
|
|
Mus musculus |
HEK-293T Cell |
| pmid |
sentence |
| 14982881 |
We report here that the Flt3-ITD interferes with the transcriptional and biologic action of the PLZF transcriptional repressor. In the presence of Flt3-ITD, PLZF-SMRT interaction was reduced, transcriptional repression by PLZF was inhibited, and PLZF-mediated growth suppression of leukemia cells was partially blocked. Furthermore, overexpression of Flt3-ITD led to a partial relocalization of SMRT protein from the nucleus to the cytoplasm. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
FLT3 | up-regulates activity
|
HK2 |
0.261 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261322 |
|
|
Homo sapiens |
Acute Lymphoblastic Leukemia Cell Line |
| pmid |
sentence |
| 28194038 |
FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3 | down-regulates quantity by repression
transcriptional regulation
|
CEBPB |
0.3 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250563 |
|
|
|
|
| pmid |
sentence |
| 16146838 |
Oncogenic mutations of Flt3 also result in the activation of aberrant signaling pathways, including strong activation of STAT5, induction of STAT target genes, and repression of myeloid transcription factors c/EBP-3 and Pu.1. |
|
| Publications: |
1 |
| Pathways: | Acute Myeloid Leukemia, miRNA in AML, FLT3-ITD signaling |
| + |
quizartinib | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258270 |
|
|
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-255666 |
|
|
in vitro |
|
| pmid |
sentence |
| 19754199 |
Compound 7 (AC220) (quizartinib) was identified from this series to be the most potent and selective FLT3 inhibitor with good pharmaceutical properties, excellent PK profile, and superior efficacy and tolerability in tumor xenograft models. |
|
| Publications: |
2 |
Organism: |
In Vitro |
| Pathways: | FLT3-ITD signaling |
| + |
FLT3 | up-regulates activity
|
PIK3R1 |
0.551 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260081 |
|
|
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 23246379 |
Grb10 transduces signal from FLT3 by direct interaction with p85 and Ba/F3-FLT3-ITD cells expressing Grb10 exhibits higher STAT5 activation. These results suggest that Grb10 binds to both normal and oncogenic FLT3 and induces PI3K-Akt and STAT5 signaling pathways resulting in an enhanced proliferation, survival and colony formation of hematopoietic cells. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
FLT3 | down-regulates quantity
transcriptional regulation
|
PTPN6 |
0.372 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259950 |
|
|
Homo sapiens |
TF-1 Cell |
| pmid |
sentence |
| 15574429 |
Furthermore, a small but reproducible growth/survival advantage was observed in both TF-1 and TF-1/ITD cells when SHP-1 expression was knocked down by RNAi. Taken together, these data provide the first evidence that suppression of SHP-1 by FLT3/ITD signaling may be another mechanism contributing to the transformation by FLT3/ITD mutations |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, FLT3 in AML, FLT3-ITD in AML |
| + |
FLT3 | up-regulates quantity by expression
transcriptional regulation
|
miR-155 |
0.4 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255796 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 25477897 |
The three miR-29 family members in mouse bone marrow cells reduced the level of TET2 as well as its metabolic by-product, 5hmC |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, miRNA in AML |
| + |
FLT3 | up-regulates quantity by expression
|
MYC |
0.371 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261556 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25280219 |
MYC expression was relatively higher (P <0Æ1) in theFLT3/ITD-positive AML samples compared to non-mutant FLT3 AML. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Acute Myeloid Leukemia, AML1-ETO in AML, FLT3 in AML, miRNA in AML, AML_TRIPLETS, FLT3-ITD in AML, FLT3-ITD signaling, Triple mutant AML, NPM1_new, WNT/FLT3 |
| + |
CHIR-124 | down-regulates
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-190976 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HES1 | down-regulates quantity by repression
transcriptional regulation
|
FLT3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261563 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 25234168 |
We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, FLT3-ITD in AML |
| + |
LSM-1231 | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258236 |
|
|
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 |
| + |
FLT3 | up-regulates activity
|
Glycolysis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259982 |
|
|
Homo sapiens |
Acute Lymphoblastic Leukemia Cell Line |
| pmid |
sentence |
| 28194038 |
Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3 | down-regulates quantity by repression
transcriptional regulation
|
BCL2L11 |
0.328 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261525 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 14981546 |
FLT3-ITD signaling contributes to transcriptional inhibition of p27Kip1 and Bim gene expression |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
linifanib | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258242 |
|
|
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 |
| + |
sorafenib tosylate | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259223 |
|
|
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 |
| + |
cabozantinib | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262242 |
|
|
Homo sapiens |
Medullary Thyroid Carcinoma Cell |
| pmid |
sentence |
| 26536165 |
Cabozantinib (XL184) is a small-molecule kinase inhibitor with potent activity toward MET and VEGF receptor 2 (VEGFR2), as well as a number of other receptor tyrosine kinases that have also been implicated in tumor pathobiology, including RET, KIT, AXL, and FLT3. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FLT3 | up-regulates activity
|
PI3K |
0.544 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260083 |
|
|
Mus musculus |
BA/F3 Cell |
| pmid |
sentence |
| 23246379 |
Grb10 transduces signal from FLT3 by direct interaction with p85 and Ba/F3-FLT3-ITD cells expressing Grb10 exhibits higher STAT5 activation. These results suggest that Grb10 binds to both normal and oncogenic FLT3 and induces PI3K-Akt and STAT5 signaling pathways resulting in an enhanced proliferation, survival and colony formation of hematopoietic cells. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | Acute Myeloid Leukemia, ASXL1 in AML, FLT3 in AML, FLT3-ITD in AML, FLT3-ITD signaling, WNT/FLT3 |
| + |
[4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-(1-piperazinyl)methanone | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258233 |
|
|
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 |
| + |
SLA2 | down-regulates activity
binding
|
FLT3 |
0.251 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256155 |
|
|
Mus musculus |
Myeloid Leukemia Cell Line |
| pmid |
sentence |
| 27458164 |
We screened a panel of SH2 domain-containing proteins and identified SLAP2 as a potent interacting partner of FLT3. We demonstrated that interaction occurs when FLT3 is activated, and also, an intact SH2 domain of SLAP2 is required for binding. Expression of SLAP2 blocked FLT3 downstream signaling cascades including AKT, ERK, p38 and STAT5. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| + |
sorafenib | down-regulates activity
chemical inhibition
|
FLT3 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258284 |
|
|
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 |
3.0
FLT3
- 
- 