| + |
regorafenib | down-regulates activity 
chemical inhibition
|
RTKs |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259453 |
|
|
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. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259452 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26254357 |
A novel multi-kinase inhibitor, regorafenib (Figure 1), inhibits vascular endothelial growth factor receptor (VEGFR) 1, VEGFR2, and VEGFR3, that play key roles in angiogenesis, and fibroblast growth factor receptor (FGFR) 1, platelet-derived growth factor receptor-β (PDGFR-β), tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (TIE2) and the mutant oncogenic kinase KIT, RET, B-RAF |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
RTKs | up-regulates activity 
phosphorylation
|
ITGB4 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259031 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30889378 |
The RTKs in turn induce phosphorylation of focal adhesion kinase (FAK) or the signaling domain of the b4 integrin. These elements recruit distinct subsets of signaling enzymes and adaptors, refining the specificity of individual partner RTKs. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Integrin Signaling |
| + |
RTKs | up-regulates activity
binding
|
PI3K |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256166 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17306385 |
Another phospholipid modifying signaling pathway activated by RTKs is the PI3K pathway. This heterodimeric enzyme comprises two subunits, the p85 regulatory subunit harboring two SH2 domains, and the p110 catalytic subunit. PI3K activation may be achieved by binding of its p85 regulatory subunit to an activated receptor. Alternatively, RTK signaling may activate the small G protein Ras, which in turn recruits PI3K to the plasma membrane and induces a stimulatory conformational change in the lipid kinase |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Integrin Signaling, PI3K/AKT Signaling, RTKs in cancer |
| + |
sorafenib tosylate | down-regulates activity
chemical inhibition
|
RTKs |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259454 |
|
|
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 |
| + |
pazopanib hydrochloride | down-regulates activity
chemical inhibition
|
RTKs |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259451 |
|
|
in vitro |
|
| pmid |
sentence |
| 17620431 |
The present study describes an orally bioavailable, ATP-competitive, multitargeted kinase inhibitor, pazopanib (GW786034), and the drug concentration requirement for maximal in vivo activity. Pazopanib is a low nanomolar inhibitor of VEGFR, PDGFR, and c-Kit tyrosine kinases. Pazopanib inhibition of a number of kinases outside of the VEGFR family was also determined. These included Abl1; Akt3; activin-like kinase 6; cyclin-dependent kinase 1/cyclin A; cyclin-dependent kinase 2/cyclin A; c-fms; c-Kit; epidermal growth factor receptor; ErbB2; ErbB4; EphB4; focal adhesion kinase; FGF receptors (FGFR) 1, 2, and 3; Flt-3; glycogen synthase kinase 3; insulin-like growth factor type I receptor; insulin receptor; interleukin-2–inducible T-cell kinase; c-jun NH2-terminal kinases 1, 2, and 3; lymphocyte-specific protein tyrosine kinase (murine); Met; p38α; PDGFRα and PDGFRβ; protein kinase C-β1 and -β2; polo-like kinases 1 and 3; Ret; Src; Syk; Tie-2; and Wee1. All assays were conducted using purified, recombinantly expressed catalytic domains of the kinases. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
GFs | up-regulates
|
RTKs |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256169 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17306385 |
Multiple growth- and differentiation-inducing polypeptide factors bind to and activate transmembrane receptors tyrosine kinases (RTKs), to instigate a plethora of biochemical cascades culminating in regulation of cell fate. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | RTKs in cancer |
| + |
RTKs | up-regulates activity
binding
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256167 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17306385 |
The adaptor protein Grb2 can bind with activated RTKs through an SH2 domain-phosphotyrosine interaction, while through the SH3 domain (a binding domain specific to proline-rich sequences) Grb2 interacts with the guanine nucleotide exchange factor, Sos. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Integrin Signaling, PI3K/AKT Signaling, RTKs in cancer |
| + |
GF | up-regulates activity
binding
|
RTKs |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256163 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17306385 |
Multiple growth- and differentiation-inducing polypeptide factors bind to and activate transmembrane receptors tyrosine kinases (RTKs), to instigate a plethora of biochemical cascades culminating in regulation of cell fate. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | PI3K/AKT Signaling, RTKs in cancer |
| + |
RTKs | up-regulates activity
phosphorylation
|
PTK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259030 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30889378 |
The RTKs in turn induce phosphorylation of focal adhesion kinase (FAK) or the signaling domain of the b4 integrin. These elements recruit distinct subsets of signaling enzymes and adaptors, refining the specificity of individual partner RTKs. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Integrin Signaling |
| + |
RTKs | up-regulates activity
phosphorylation
|
A6/b4 integrin |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259032 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30889378 |
The RTKs in turn induce phosphorylation of focal adhesion kinase (FAK) or the signaling domain of the b4 integrin. These elements recruit distinct subsets of signaling enzymes and adaptors, refining the specificity of individual partner RTKs. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Integrin Signaling |
3.0
RTKs