By Lorenzo A. Pinna, Patricia T.W. Cohen
The goals of this volume are to focus on the super pharmacological strength of protein kinase and protein phosphatase inhibitors, to supply a radical review of the main outstanding achievements within the box and to demonstrate how worthwhile those reports should be for the development of either simple wisdom on organic rules and deregulation and for the medical remedy of a large spectrum of ailments. This goal is attained via contributions of chief investigators within the box, who address the problem from assorted angles.
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Extra info for Inhibitors of Protein Kinases and Protein Phosphates
Example text
Future Development of Paullones . . . . . . . . . . . . . . 54 55 57 59 4 Conclusion . . . . . . . . . . . . . . . . . . . 60 References . . . . . . . . . . . . . . . . . . . . . 60 . . . . . . . . . . . . . . Abstract Cyclin-dependent kinases (CDKs) regulate multiple pathways such as the cell division cycle, apoptosis, transcription, and neuronal functions. ” Both families of kinases are clearly involved in the onset and development of major human diseases like cancer, neurodegenerative disorders (Alzheimer s and Parkinson s disease, stroke), diabetes, restenosis, viral infections, etc.
However, the doubly substituted Gly-Ile-Nal-Trp-His-HisNal exhibits an IC50 of 4 M, suggesting that the C-terminal Nal is able to access sites outside of the immediate active site region. Interestingly, one of the less effective inhibitors Gly-Ile-Nal-Trp-His-His-Tyr (IC50=27 M) proved to be remarkably selective for Src versus other closely related members of the Src kinase family (Lyn and Lck; IC50>1 mM). One of the difficulties associated with the acquisition of nonphosphorylatable tyrosine surrogates is their synthesis, which typically resorts to the use of achiral starting material.
Discovery of Paullones . . . . . . . . . . . . . Molecular Mechanism of Interaction of Paullones with Kinases— Structure/Activity Relationship Studies . . . . . . . . Selectivity of Paullones . . . . . . . . . . . . Cellular Effects of Paullones . . . . . . . . . . . Future Development of Paullones . . . . . . . . . . . . . . 54 55 57 59 4 Conclusion . . . . . . . . . . . . . . . . . . . 60 References . . . . . . .