Kinase research programs

BMS-354825, which has the generic name of dasatinib, entered Phase II clinical trials in December 2004 under the START (Src/Abl Tyrosine kinase inhibition Activity Research Trial) program [ 144-147]. Dosing was initiated at 70 mg twice daily with the option of increasing the dose to 90 or 100 mg or reducing the dose to 40 or 50 mg, depending on low response or toxicity. As part of the Phase I and II trials, patients were assessed for the presence of Bcr-Abl mutations prior to treatment with BMS-354825. In a study at UCLA,... 

Parallel to our group, a few other researchers also performed significant studies on anticancer (3-lactams. For example, (3-lactam derivatives (Fig. 2) induced DNA damage, inhibited DNA replication, and activated the apoptotic death program in human leukemic Jurkat T cells in a time and concentration-dependent manner. Importantly, (3-lactam 69 also inhibited proliferation and induced apoptosis in other human solid tumor cell lines (breast, prostate, and head-and-neck). It was believed that induction of apoptosis by 69 is associated with activation of p38 mitogen-activated protein (MAP) kinase, release of mitochondrial cytochrome c, and activation of the caspases. It was reported that apoptosis is blocked by a specific inhibitor to p38 kinase, implicating p38 MAP kinase as the major factor in (3-lactam-induced apoptosis [154]. This study was very significant. 

An example demonstrates some of the power and scope of this tool for biological literature analysis. Imagine a researcher is studying the apoptotic cysteine protease, caspase 3. To understand how this protease regulates programmed cell death, the researcher might want to explore which serine/threonine kinases are substrates for the enzyme (i.e., are cleaved by caspase 3). Figure 6.8 shows how the researcher... 

Studies indicate that IGF-1 protection is induced via activation of protein kinase B Akt (Franke et al, 1995 Alessi et al, 1997 Dudek et al, 1997 Nunez del Peso, 1998). In the case of IGF-1 a great deal of research has shown that it has neuroprotective properties, reducing programmed cell death of motor neurons (Lewis et al, 1993) and... 

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