| + |
afatinib | down-regulates activity 
chemical inhibition
|
ErbB receptor family |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259441 |
|
|
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-259442 |
|
|
Homo sapiens |
Breast Cancer Cell |
| pmid |
sentence |
| 22418700 |
Afatinib is an oral, erbb family blocker, which covalently binds and irreversibly blocks all kinase-competent erbb family members. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259443 |
|
|
Homo sapiens |
Non-small Cell Lung Cancer Cell |
| pmid |
sentence |
| 24643470 |
This manuscript comprehensively reviews the preclinical data on afatinib, an irreversible inhibitor of the tyrosine kinase activity of members of the epidermal growth factor receptor family (ErbB) including EGFR, HER2 and ErbB4. Afatinib covalently binds to cysteine 797 of the EGFR and the corresponding cysteines 805 and 803 in HER2 and ErbB4, respectively. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259440 |
|
|
Homo sapiens |
Lung Cancer Cell |
| pmid |
sentence |
| 22452896 |
Afatinib, an irreversible erbb-family blocker, has shown preclinical activity when tested in egfr mutant models with mutations that confer resistance to egfr tyrosine-kinase inhibitors. |
|
| Publications: |
4 |
Organism: |
In Vitro, Homo Sapiens |
| + |
LRIG1 | down-regulates
ubiquitination
|
ErbB receptor family |
0.727 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269872 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16123311 |
We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EGFR | up-regulates 
binding
|
ErbB receptor family |
0.655 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269876 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11279155 |
These results demonstrate that egfr-erbb2 oligomers are potent activators of mapk and akt, and this signaling does not require egfr kinase activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA) |
| + |
ErbB receptor family | up-regulates activity
binding
|
PI3K |
0.773 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256168 |
|
|
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: | ErbB receptors in cancer, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), RTKs in cancer |
| + |
dacomitinib | down-regulates
chemical inhibition
|
ErbB receptor family |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269871 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23405260 |
The goal of this study was to compare dacomitinib (pf-00299804), a next generation small molecule tyrosine kinase inhibitor that irreversibly blocks multiple her family receptors (her-1 (egfr), her-2 and her-4 tyrosine kinases), to cetuximab, the current fda approved anti-egfr medication for hnscc and erlotinib, an egfr specific small molecule tyrosine kinase inhibitor. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
sapitinib | down-regulates
chemical inhibition
|
ErbB receptor family |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269874 |
|
|
Homo sapiens |
Lung Cancer Cell |
| pmid |
sentence |
| 20145185 |
In vivo, azd8931 inhibited xenograft growth in a range of models while significantly affecting egfr, erbb2, and erbb3 phosphorylation and downstream signaling pathways, apoptosis, and proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ErbB receptor family | up-regulates activity
binding
|
GRB2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256162 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14967450 |
All erbb ligands and receptors couple to activation of the ras-mapk pathway, either directly through sh2 domain-mediated recruitment of grb-2 or indirectly through ptb domain-mediated binding of the shc adaptor |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | ErbB receptors in cancer, Non-small-cell lung cancer (NSCLC), RTKs in cancer |
| + |
NRG1 | up-regulates
binding
|
ErbB receptor family |
0.904 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269870 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 14967450 |
The neuregulins (also called heregulins and neu differentiation factors) nrg-1 and nrg-2 bind erbb-3 and erbb-4;and nrg-3 and nrg-4 bind erbb-4. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ERBB2 | up-regulates activity
phosphorylation
|
ErbB receptor family |
0.61 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269875 |
|
|
in vitro |
|
| pmid |
sentence |
| 1706616 |
 Y1023 and Y1248, Y1139 and Y1222 also serve as autophosphorylation sites of HER2. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
EREG | up-regulates
binding
|
ErbB receptor family |
0.891 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269873 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16829981 |
For example, betacellulin binds to and activates both erbb1 and erbb4, whereas epiregulin binds to erbb1, erbb3 and erbb4. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ErbB receptor family | up-regulates
relocalization
|
SHC3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-269962 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16729043 |
Like erbb1, erbb4 recruits grb2, shc and stat5. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Neuregulin | up-regulates activity
binding
|
ErbB receptor family |
0.906 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256161 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18415007 |
The neuregulin family consists of four genes, NRG1-4 which can each encode products containing a domain related to the epidermal growth factor family of ligands. they may be released by regulated proteolysis to act as soluble proteins which can interact and activate members of the EGF receptor family of receptor tyrosine kinases |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | ErbB receptors in cancer |
3.0
ErbB receptor family