Zus Tzlich although the PLK1 depletion is t Harmful for cancer cells showed normal cells little or no cytotoxicity t In response to Ersch Shrinkage. BIIB021 CNF2024 Thus, PLK1 is an attractive target for anti-mitotic cancer therapies. The first small molecule inhibitor of Plk1 was reported marine natural product compounds scytonemin.96 ON01910.Na BI 2536 and are currently in clinical development. BI 2536 BI 2536 is highly selective for PLK1. Investigated in Phase I trial in 104 patients 2 different regimens evaluated.97, 98 The main dose-limiting toxicity of t The two calendars was neutropenia. With the addition of thrombocytopenia on the lists Other side effects were fatigue, nausea and vomiting. The phase II trials evaluating BI 2536 are underway in metastatic or recurrent non-small cell lung cancer and small cell lung cancer as second-line therapy.
ON 01910.Na 01910.Na is a competitive inhibitor of ATP PLK1, the st with the F ALK Inhibitors Ability, substrates bind PLK Rt. It has nanomolar potency against ABL, FLT1 and PDGFR.84 In phase I studies, three different treatments were evaluated and the results pr in abstract form Presents on these.99 2, 100 events events were mild to moderate Mie, leukopenia erh hte liver enzymes, the symptom My stomach and fatigue. KSP kinesin spindle protein inhibitors is a motor protein kinesin which then causes it the separation of the centrosome and is required to produce the bipolar spindle. There is evidence that increased CSF expression in tumor cells compared to normal cells Ht. 101 inhibition of KSP causes mitotic arrest with monopolar spindle no effect on proliferating cells.
84 KSP absent in differentiated neurons. The first small molecule selective inhibitor of KSP KSP inhibitors have been identified monastrol.102 POWERFUL Higer since been identified, including normal ispinesib furthest advanced in clinical trials. Ispinesib ispinesib is a small molecule 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 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 m