mitosis5Ormation of the mitotic spindle in early mitosis.5 Centromeric protein E is necessary for accurate congression w During metaphase.6 A better amplifier Ndnis these mediators mitosis and r Them in tumor development has led the expansion of efforts to target mitosis by other means CX-4945 in addition to the St Mitotic spindle microtubules by binding tion. Focus on intensive research targeted agents such as anti-cancer therapies, with the focus now not mitotic microtubules, such as kinases and kinesins as m Possible targets. This review will focus on new active substances which. Concentrate against the spindle microtubules during mitosis elements and concepts that are not effectors of microtubules in mitosis Discussions seem to focus on this promising agent sp Th clinical development.
Epothilones epothilones whole are most advanced in clinical BMS-754807 development of a new class of mitotic inhibitors. Their mechanism of action and the biological activity of t are rated good elsewhere. 7 The 16-k Pfige macrolide ring with a chain Methylthiazole page not isolated from the myxobacteria Sorangium cellulosum. natural epothilones as epoxies or olefins.8 They compete with paclitaxel for binding to microtubules and seem to suppress microtubule dynamics in the same fa there classified as paclitaxel. 11th September, with IC50 concentrations in the nanomolar range, epothilones have much more power taxanes.7 cytotoxic, 11, 12 Different mechanisms of resistance, including normal tubulin mutations and overexpression of multidrug resistance proteins or tubulin III to give a low resistance epothilones.
7, 13, 16 in an effort to enhance the anti-tumor efficacy, epothilone analogs were synthesized. Changes Ver Such as synthetic forms Change Including both pharmacological and biological properties Lich antitumor activity of t And L Solubility. 17, 18 epothilone B, a natural product, and some of its synthetic derivatives, including normal Ixabepilone, BMS 310705, ZK EPO and epothilone D in clinical development for the treatment of cancer. Patupilone patupilone is twice st Induce stronger than epothilone A or paclitaxel on tubulin polymerization in vitro.7, 11 the dose-limiting toxicity Diarrhea t in the three systems of administration in the phase I trials, 19′s, 20 , in contrast to other epothilones. Fatigue and nausea and vomiting are less frequent and significant neuropathy was rare.
Since patupilone is metabolized by carboxylesterase one, with the P-450 system plays an r The minimal tissue Esteraseaktivit t can play an r Important in determining the toxicity of t of profile.7, 21 In Phase II has promising activity t in the lungs, 22 24 ovarian cancer, 25 and renal cancers.26 However, no reaction was observed in patupilone in neuroendocrine tumors, 27 showed , but there was a high level of stable disease. Minimum reaction time was in colorectal carcinomas, 28, 29 hepatocellular Ren, 30 and gastrointestinal tumors.31 A phase III study of doxorubicin versus observed
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