Similarly,
inhibiting ABL kinase activity with the allosteric inhibitor GNF5 decreased TAZ protein abundance (fig.
Axitinib, a drug used to treat renal cell carcinoma, has been shown to be effective at
inhibiting the Abl kinase activity in patients with BCR - ABL1 (T315I).
[citation needed] In 2000 Dr. John Kuriyan determined the mechanism by which STI - 571
inhibits the Abl kinase domain.
Not exact matches
Therefore, a team led by Vladimir Tesar, MD, PhD (Charles University and General University Hospital, in the Czech Republic) tested the potential of an investigational drug called bosutinib that
inhibits a particular tyrosine kinase called Src / Bcr -
Abl.
The BCR -
ABL inhibitor ponatinib
inhibits platelet immunoreceptor tyrosine - based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear.
Activated
Abl kinase
inhibits oncogenic transforming growth factor - β signaling and tumorigenesis in mammary tumors.
In addition to
inhibiting STAT5 signaling, we found that depletion of
ABL kinases decreased the expression of the Hippo pathway mediator TAZ and downstream target genes in triple - negative and HER2 + breast cancer cells.
Depletion of
ABL kinases does not
inhibit metastasis of 4175 breast cancer cells, which show tropism to the lung.
Inactivation of
ABL kinases
inhibited the expression of the TAZ target gene AXL, which shows increased expression in several human cancers and correlates with poor prognosis, increased invasiveness and metastasis, and enhanced drug resistance (53, 54).
We found that ~ 90 % knockdown of
ABL1 alone resulted in enhanced
ABL2 expression and did not produce a significant decrease in the phosphorylation of CrkL, a reporter for the activation state of the
ABL kinases (Fig. 2K), and did not
inhibit metastasis (Fig. 2, L and M).
In addition to RIPK2 binding as part of this computer - based (initial) screening, we selected compounds that
inhibited epidermal growth factor receptor (IC50 values > 1000 nM; weak inhibitory activity) along with weak binding interactions in the EGFR and c -
ABL binding sites, two common off - targets for previously identified RIPK2 inhibitors.