Ucn01

UCN-01 is a cell-cycle modulator with a number of complex effects resulting in both G1/S arrest and aberrant entry into M phase. These cell-cycle kinetics are associated with an increased p27kip2-cdk2 interaction, Rb hypophosphorylation, and cdkl activation due to chkl inhibition. Phase I trials examined a 72-hour continuous infusion schedule, with dose-limiting toxicities that included nausea, hypotension, hyper-

glycemia, and pulmonary toxicity, and evidence for activity was seen in two patients with melanoma and lymphoma.

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