Molecular Mechanisms of Microtubule Acting Cancer Drugs

摘要: Here the molecular mechanism of antimitotic drugs, biological compounds that bind to tubulin and microtubules suppress microtubule dynamics are reviewed. A common feature tubulin-interacting is binding linked assembly, either stabilization a lattice by like taxanes epothilones, or induction alternate, nonmicrotubule polymer forms. The polymers arise from heterodimers at ends with colchicine, vinca alkaloids, dolastatin, cryptophycin-52. Their action strongly coupled especially structural features affect nucleotide binding, GTP hydrolysis, longitudinal lateral protofilament contacts, endwise growth disassembly dynamics. Quantitative analysis drug formation can be useful tool in design, as many cases energetics predictive IC50 values clinical doses. Furthermore, these drugs allosterically disrupt regulation dynamics, whereas regulatory factors themselves may play an important role resistance. Thus, development selectively target mitotic spindle kinetochore capture, chemical genetics for example, result effective therapeutic tools.