Targeting protein kinases in cancer therapy with irreversible small-molecule inhibitors is moving to the forefront of kinase-inhibitor research and is thought to be an effective means of overcoming mutation-associated drug resistance in epidermal growth factor receptor kinase (EGFR). We generated a ...
Davis et al. extend their previous efforts to use inhibitor-kinase interactions to understand kinase inhibitor selectivity by profiling the binding of 72 kinase inhibitors to 442 human kinase catalytic domains. The data reveal group-specific differences
Integration-free reprogramming of cancer cells would be safer and preferable for clinical use. Along those lines, we screened a kinase inhibitor library and found that a combination of the inhibitors for two kinases, Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR), c...
Through screening a small molecule compound library developed for the phosphatidylinositol 3'-kinase-like kinase family, we identified an ATP-competitive inhibitor, 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one (KU-55933), that inhibits ATM with an IC(50) of 13 nmol/L and a Ki of 2.2...
In this study, we report the generation and characterization of five novel analogs of the PKD inhibitor CID755673. This compound, previously identified as a novel PKD inhibitor, inhibited PKD1 with an IC50 of 182 nM in vitro, and blocked cancer-associated properties of prostate cancer cells. Th...
Because high affinity binding of imatinib requires a flipped DFG motif (40), the nonsynonymous Ala/Ser substitution may contribute to this conformational change and negatively influence inhibitor binding. As results from Y2H library screening schistosome homologs of the known Src kinase SmTK3 (15), ...
strategy to identify this kinase. Using a combination of screening a library of 65'000 kinase inhibitors and in vitro inhibitor target profiling of the screening hits using the Ambit kinase platform, MKK4 was identified as playing a key role in Tau-S422 phosphorylation in human neuroblastoma ...
In this work, we evaluated the sensitizing effect of sitravatinib, a broad‐spectrum tyrosine kinase inhibitor (TKI), on ATP‐binding cassette subfamily B member 1 (ABCB1)‐ and ATP‐binding cassette subfamily C member 10 (ABCC10)‐mediated MDR....
et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 7, 129–141 (2005). Article CAS PubMed Google Scholar O'Farrell, A. M. et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101,...
(Fig.4a). To investigate how URI upregulates SCD1 expression in cancer cells, we first examined the effect of URI on the protein stability of SCD1. MG132, a proteasome inhibitor, did not increase the protein levels of SCD1 in shURI cells (Supplementary Fig.5a). Consistently, the ...