Microtubule-targeting drugs

Microtubule Dynamics and its Modulation by Microtubule-Targeted Drugs and regulatory proteins... 

Modulation of microtubule dynamics by microtubule-targeted drugs... 

Lee, E. A, Keutmann, M. K, Dowling, M. L., Harris, E., Chan, G., Kao, G. D. (2004). Inactivation of the mitotic checkpoint as a determinant of the efficacy of microtubule-targeted drugs in killing human cancer cells. Molecular Cancer Therapeutics, 3, 661-669. 

Gibson S, Widmann C, Johnson GL. Differential involvement of MEK kinase 1 (MEKKl) in the induction of apoptosis in response to microtubule-targeted drugs versus DNA damaging agents. J Biol Chem 1999 274(16) 10916-10922. 

Beck WT, Cass CE, Houghton PJ. Microtubule-targeting anticancer drugs derived from plants and microbes vinca alkaloids, taxanes, and epothiolones. In Bast RC Jr, Kufe DW, Pollock RE, Weichselbaum RR, Holland JF, Frei E III, eds. Holland-Frei Cancer Medicine. 5th Ed. Hamilton, Ontario BC Decker, 2000 680-698. 

Microtubule-targeting agents are amply used in chemotherapy and recent evidence suggests that they require of mitochondria for their anti-cancer effectiveness (Figure 6). Microtubule-destabilizing drugs such as alkaloids colchicine (used for gout treatment and familial mediterranean fever [162]) and nocodazole produce increase of free tubulin and in parallel decrease of Av /m in human hepatoma cells [163], In contrast, decrease of free tubulin... 

Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004 4 253-265. 

Microtubules in cells undergoing mitosis are the target of several important drugs. One of these is the alkaloid colchicine which is produced by various members of the lily family and has been used since ancient Egyptian times for the alleviation of the symptoms of gout.a b... 

Many attempts have been made over the last years to deduce the actual pharmacophore/s for the recognition of MSA by microtubules. For newly designed MSA to serve as effective anticancer drugs, it seems reasonable that they should be able to achieve a conformation compatible with the binding pocket of the target protein. On this basis, many scientists have focused on determining the bioactive conformation of the different MSAs. 

Antimitotic drugs that target microtubules (MT) or its constituent protein tubulin are one of the most successful classes of anticancer agents discovered so far. MT are long, filamentous, tube-shaped protein polymers that are essential in all eukaryotic cells. Antimitotic agents are compounds that arrest cells in mitosis, which results in the slowing or blocking of mitosis and induction of apoptotic cell death. 

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