was identified were identified monastrol.102 st Strongest KSP inhibitors, including normal ispinesib most advanced in clinical trials. Ispinesib ispinesib is a small molecule ITMN-191 inhibitor of KSP ATPase, which were not in competition with ATP and ADP and 40,000 times more selective for KSP than any other kinesins.103 In phase I studies, 3 Zeitpl Ne evaluated.104 106 Main dose-limiting toxicity t was neutropenia. Other side effects were leukopenia, An Chemistry and fatigue. In phase II studies, has ispinesib activity t in patients with metastatic breast cancer who have relapsed or shown progress after treatment with an anthracycline and taxane.107 Unfortunately, it has no activity T seen in cancer, 108 hepatocellular Ren, head and neck, 109, 110, ovarian 111 or renal cell carcinoma, 112 or melanoma.
113 studies in non-small cell lung cancer cells and prostate cancer were conducted hormonerefractory, but results have not been reported. Phase I trials in patients with malignant h Dermatological diseases are currently pro Habits. Ispinesib was generally well tolerated with mild h Hematological toxicity th 17-AAG Tolerated and a few others. Other mitotic inhibitors SB 743921 is an inhibitor of kinesin KSP m Most powerful ispinesib.114 The main dose-limiting toxicity t is neutropenia, the onset and duration in Phase I predictable.115 II Phase I trials are underway in non-Hodgkin’s Lymphoma. GSK 923295 is an inhibitor of protein E. centromere CENPE is a component of the mitotic checkpoint, congression of chromosomes on the equator Catalyzes the spindle before biorientation.
6 A phase I study in patients with advanced solid tumors are ongoing. Conclusion The development of new drugs for the treatment of cancer is a dramatic paradigm shift. Much emphasis is. On therapeutics produced on specific molecular targets in tumor cells, as opposed to non-specific cytotoxic chemotherapies, which placed all of the cells that affect a division contrast Part of this paradigm shift is on a better amplifier Ndnis the biology of the tumor and the involvement of cancer as a chronic disease. Thus minimizing toxicity t with tumor-specific targets is of great importance he. The only exception is the continuous development of agents that target mitotic tubulin and microtubules that.
Relatively less selective for cancer cells, mitotic kinases and associated targets and kinesins, which seem to be more selective for cancer cells The FDA approval of ixabepilone in Era of targeted therapy is an exciting development. Its success lies in the F Ability, resistance to overcome the taxanes hampered w While one Similar broad antitumor activity. However, the problems remain and the formulation of Neurotoxizit t difficult. n HIGHEST generation epothilones and anti-microtubule agents are promising to address these problems, but only those authorized are antimitotic tubulin as their target. Mitotic kinase ki