Cell signaling inhibitors

Antimicrobials and Antibiotics Specific metabolic inhibitors, electrophilic organics, cell signaling inhibitors Nonoxidizing Biocides... 

This section deals with the basic approaches to treating cells with hormones (or other agents) and with signaling inhibitors, and for the lysis of cells after treatment. 

In many cases, signaling inhibitors may affect the basal rate of protein synthesis. It is crucial to take this into account when evaluating their effects on the activation of protein synthesis, and appropriate controls must be carried out to assess the effects of the inhibitors on the rate of protein synthesis in unstimulated cells. Two other important points are (i) that assays must be performed at least in duplicate and (ii) that cells should be no more than 85% confluent. 

Triciribine, also known as Akt/protein kinase B signaling inhibitor-2 (API-2) compound 52, Fig. 9), was identified by screening the National Cancer Institute Diversity Set chemical library (1992 compounds). The screen was performed using a cell-based proliferation assay with PKB/1 transformed NIH3T3 cells, and triciribine scored positive in this assay with an IC50 value of 50 nM [ 196]. Although the compound blocks the cellular phosphorylation... 

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Introduction Cyclooxygenase-2 Antiangiogenesis Agents Signal Transduction Inhibitors Ras Farnesylation Inhibitors Cell Cycle Inhibitors Promotors of Apoptosis Conclusions References... 

Schulte G, Fredholm BB (2002a) Diverse inhibitors of intracellular signalling act as adenosine receptor antagonists. Cell Signal 14(2) 109-113... 

Actinomycin D has been clinically used for the treatment of many cancers and is known to be a DNA intercalator. The structure of actinomycin D is based on a phenoxazine ring bound to two cyclic pentapeptides [33]. The presence of the phenoxazine ring in the structure of actinomycin D suggests that phenoxazine derivatives may possess anticancer activity. Phenoxazine derivatives are known to be effective multidrug resistance (MDR) modulators in cancer cells [34], potent inhibitors of Akt signaling in cells [35], inhibitors of human plasma cholinesterase [36], and photo-chemotherapeutic agents in cancer cells [37]. Recent studies also show that the relatively water-soluble phenox-azines, such as 2-amino-4,4a-dihydro-4a,7-dimethyl-2H-phenoxazine-3-one and 2-aminophenoxazine-3-one, exert antitumor effects on various cancer cells in vitro and in vivo. [38]. We have investigated 24 phenoxazines [23,39] (Fig. 4). 

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