Sentences with phrase «abl inhibitor»

This discovery led him to evaluate second generation Abl kinase inhibitors, such as the dual Src / Abl inhibitor dasatinib, which received fast - track approval at the FDA in June 2006.

(B) Survival of mice after intracardiac injection of 1833 (1 × 105) breast cancer cells and treatment with either dimethyl sulfoxide (DMSO) control or the allosteric ABL inhibitor GNF5.

The BCR - ABL inhibitor ponatinib inhibits platelet immunoreceptor tyrosine - based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear.

Not exact matches

In experiments on cell cultures, both of these inhibitors succeeded in breaking various forms of the TKI resistance: including forms caused by additional mutations of the gene Bcr - Abl as well as those caused by large quantities of the protein Gab2.

An approach often used in treating CML is to block the Bcr - Abl activity using tyrosine kinase inhibitors (TKIs).

Imatinib is an inhibitor that blocks the ATP - binding site of the tyrosine kinase Abl in affected blood cells, thereby suppressing their overactivity.

Abrogation of the cell death response to oxidative stress by the c - Abl tyrosine kinase inhibitor STI571.

Similarly, inhibiting ABL kinase activity with the allosteric inhibitor GNF5 decreased TAZ protein abundance (fig.

The allosteric inhibitors specific for ABL kinases (which are currently in clinical trials) provide a potentially useful tool for selectively targeting ABL kinases in metastatic breast cancer types with an increase in the ABL pathway signature (58).

Moreover, we found that treatment with a selective allosteric inhibitor of the ABL kinases or simultaneous depletion of both ABL kinases in breast cancer cells impaired breast cancer bone metastases and decreased osteoclast activation in vitro and osteolysis in vivo.

Together, our data suggest that clinical studies may be warranted to evaluate the therapeutic potential of ABL allosteric inhibitors and to determine whether combination therapies that incorporate these compounds are effective in treating metastatic breast cancer.

These mutant kinases are attractive therapeutic targets, as demonstrated by the efficacy of imatinib in BCR - ABL — positive chronic myelogenous leukemia (CML), 5 as well as in MPD associated with activating alleles involving PDGFRA or PDGFRB.2, 6,7 In addition, activating mutations in the FLT3 receptor tyrosine kinase are the most common genetic event in acute myeloid leukemia (AML), and specific inhibitors of the FMS - like tyrosine kinase 3 (FLT3) have entered late - stage clinical trials.8 Although mutations in tyrosine kinases and in other genes have been identified in a subset of MPD and AML, in many cases the genetic events that contribute to the molecular pathogenesis of these diseases remain unknown.

IC50 for c - ABL for both inhibitors is > 100 μM.

This rules out the possibility that resistance to inhibitors results from a steric hindrance as proposed for the Thr315 mutations of ABL.13, 33 However, the crystal structures of JAK1 and JAK2 also show that Phe958 or Tyr931, respectively, are in direct contact with the CMP6 inhibitor.21 The replacement of Phe958 by Val / Cys / Ser / Leu abolishes this interaction and should decrease the affinity for this compound (Figure 2C).

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.

Because of robust off - target effects of most RIPK2 inhibitors, we carried out molecular modeling (docking) and cheminformatics analyses by carefully analyzing the only known crystal structure of RIPK2 in association with the c - ABL kinase inhibitor ponatinib (https://www.rcsb.org/pdb/explore/macroMoleculeData.do?structureId=4C8B).

This work, and that of colleagues Brian Druker and Novartis, led to the development of the kinase inhibitor imatinib (Gleevec) as primary therapy for chronic myelogenous leukemia (CML), and the discovery that imatinib resistance is caused by BCR - ABL kinase domain mutations.