Tyrosine-specific kinase inhibitor

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

Protein kinases can be classified according to the amino acid residue that is phosphorylated in the cellular process. Consequently, there are tyrosine-specific kinases and serine/threonine kinases. Tyrosine kinases are a family of tightly regulated enzymes, and the aberrant activation of various members of this family is one of the hallmarks of cancer. Tyrosine phosphorylation has been linked to multiple cell growth and differentiation pathways. Imatinib mesylate (1) is a tyrosine kinase inhibitor (TKI). An important characteristic of imatinib mesylate (1) is that it is an ATP-competitive inhibitor. It binds at the ATP binding site and blocks ATP binding thereby inhibiting kinase activities. 

Genistein, a specific inhibitor of tyrosine-specific protein kinases. JBiol Chem. 262 5592-5. 

There are more than 100 different types of tyrosine kinases present in the body. Sometimes tyrosine kinase inhibitors are referred to as small-molecule inhibitors. Each of the following drugs was developed to block either several or a specific tyrosine kinase. 

Tyrosine kinase inhibitor relatively specific for the tyrosine kinase coded for by the bcr-abl translocation in CML patients... 

Schmidt It is thought to be Cdk4-specific, but it comes out of screens for general tyrosine kinase inhibitors. It seems to be the most specific, and it is the furthest along, so you could probably obtain it more easily. 

Protein Kinase Inhibitors Pseudosubstrate-based peptide inhibitors, 201, 287 utilization of the inhibitor protein of adenosine cyclic monophosphate-dependent protein kinase, and peptides derived from it, as tools to study adenosine cyclic monophosphate-mediated cellular processes, 201, 304 use of sphingosine as inhibitor of protein kinase C, 201, 316 properties and use of H-series compounds as protein kinase inhibitors, 201, 328 use and specificity of staurosporine, UCN-01, and calphostin C as protein kinase inhibitors, 201, 340 inhibition of protein-tyrosine kinases by tyrphostins, 201, 347 use and specificity of genistein as inhibitor of protein-tyrosine kinases, 201, 362 use and selectivity of herbimycin a as inhibitor of protein-tyrosine kinases,... 

On May 10, 2001, the FDA approved a Novartis drug, Gleevec, a tyrosine kinase inhibitor that specifically targets the BCR/ABL fusion protein. 

Akiyama, T., Ishida, J., Nakagawa, S., Ogawara, H., Watanabe, S., Itoh, N., Shibuya, M., and Eukami, Y., Genistein, a specific inhibitor of tyrosine-specific protein kinases, J. Biol. Chem., 262, 5592, 1987. 

Yang, E.B. et al., Butein, a specific protein tyrosine kinase inhibitor, Biochem. Biophys. Res. Common., 245, 435, 1998. 

Fry DW, Bridges AJ, Denny WA et al. Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor. Proc Natl Acad Sci USA 1998 95 12022-12027. 

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