protein kinases have become a major class of drug targets. Since the first kinase inhibitor, imatinib, was approved by the FDA in 2001 for the treatment of chronic myeloid leukemia, there have been 82 FDA-approved small-molecule protein kinase inhibitors as of September 2024, predominantly used ...
kinase inhibitor drug discovery has progressed dramatically in the past decade. Clinical evaluation of kinase inhibitors has shown that therapeutic responses vary widely in individual patients and across patient populations, and seem to depend on many diverse factors. Many new candidate molecules have ent...
Even though only a small fraction of the kinome is currently being targeted, kinase inhibitor drug discovery has progressed dramatically in the past decade. Clinical evaluation of kinase inhibitors has shown that therapeutic responses vary widely in individual patients and across patient populations, and...
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
Making sense of large-scale kinase inhibitor bioactivity data sets: a comparative and integrative analysis. J. Chem. Inf. Model. 54, 735–743 (2014). Article Google Scholar Pahikkala, T. et al. Toward more realistic drug–target interaction predictions. Brief. Bioinform. 16, 325–337 (...
LMTK3;kinase inhibitor;breast cancer 1. Introduction Protein kinases are a large family of enzymes responsible for catalyzing protein phosphorylation. They are involved in critical mechanisms regulating different cellular functions, including proliferation, cell cycle, apoptosis, motility, growth, and differ...
(Thr69/71) of the downstream target pATF2 in pEMT cells. Subsequently, the p-p38 inhibition resulted in reduced Slug protein levels. In accordance, p-p38 inhibition led to sensitization of pEMT cells to cisplatin-induced cell death; moreover, p-p38 inhibitor treatment cycles significantly ...
Treatment of this disease with imatinib, a specific inhibitor of Abl, has established a paradigm for targeted therapy in cancer.32 Abl is a nonreceptor tyrosine kinase that contains Src-homology 3 and 2 (SH3 and SH2) domains in addition to its tyrosine kinase domain. Additionally, the ...
A drug resistance screen using a selective MET inhibitor reveals a spectrum of mutations that partially overlap with activating mutations found in cancer patients. Cancer Res. 2011;71(15):5255–64. Article CAS Google Scholar Engstrom LD, Aranda R, Lee M, Tovar EA, Essenburg CJ, Madaj Z, ...
Here we show that LAM-003, a prodrug of the heat shock protein 90 inhibitor LAM-003A, has cytotoxic activity against AML cell lines and primary samples harboring FLT3-ITD. LAM-003 regressed tumors in an MV-4-11 xenograft mouse model and extended survival in a MOLM-13 systemic model. LAM...