Vinca site binding agents

VINCA SITE BINDING AGENTS Vinca Alkaloids... 

Fig. 9 Chemical structures of different Vinca site binding agents...

Vinca alkaloids (vincristine, vinblastine, vinorelbine) are derived from the periwinkle plant (Vinca rosea). These agents work by binding to tubulin at a site different than colchicine or paclitaxel. They block polymerization, which prevents the formation of the mitotic spindle, and are used as antineoplastic agents. Taxanes produce a stabilization of microtubules similar to colchicine, but by a different mechanism, and also halt cells in metaphase. Paclitaxel (taxol) is the taxane used clinically. It is derived from the bark of the pacific yew. Taxol disrupts several microtubule-based functions as completely as inhibitors of polymerization, emphasizing the importance of assembly/disassembly balance in microtubule function. Recently, it has been found that paclitaxel also binds to and inhibits the function of a protein called bcl-2, an inhibitor of one or more pathways involved in mediating apoptosis. PaclitaxeTs interference with this function promotes apoptosis in addition to its microtubule-related inhibition of cell division. 

This molecule, like its parent, is a tubulin interactive agent with very potent activity at the nanomolar level in in vitro studies and binding at or close to the vinca site from recent modeling studies. Much fuller details of the synthetic and base biological information were published by the leaders of the studies in 2005, and recently a short article covering the basic details but including the latest clinical citations was published by Wang. These two articles should be read by the interested reader for fuller details of the evolution of this compound. 

Bai, R.L., G.R. Pettit, and E. Hamel. 1990. Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and Vinca alkaloid sites./. Biol. Chem. 

Most MT-Destabilizing Agents Bind to the Colchicine Site or to the Vinca Domain of Tubulin... 

Other binding sites have been postulated according to tubulin interfering agents with a binding behaviour distinct to that of taxanes, vinca alkaloids and colchinoids. 

Known antimitotic agents (see Fig. 2) bind to a number of characterized sites on the tubulin protein. The most well characterized sites include the taxol binding site, the vinca alkaloid domain and the colchicine site. 

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