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[摘要]：ON 07970.Na (rigosertib, Estybon (R)) is a novel small molecule developed to treat cancer. It has a multitargeted mechanism of action, including polo-like kinase inhibition, resulting in selective blockade of mitosis and death in cancer cells, even those carrying drug-resistant mutations. In preclinical experiments, ON 07970.Na proved active against numerous cancer types both alone and in combination with other chemotherapies. Pharmacokinetic studies show that the compound undergoes rapid plasma elimination (t(1/2) < 1 hour), with limited evidence of metabolism but extensive biliary excretion. Over 260 patients have been treated with intravenous ON 01910.Na in clinical trials, and the compound showed a good safety profile, with a low incidence of adverse events. The lead indication is myelodysplastic syndrome (MDS), and ongoing studies show favorable results in MDS patients. The US. FDA has designated ON 01910.Na as an orphan drug for the treatment of MDS and has provided a Special Protocol Assessment, accepting a pivotal phase III trial design for monotheropy in patients with MDS refractory to hypomethylating agents. Additional hematological and solid tumor (e.g., acute myeloid leukemia, ovarian and pancreatic cancer) indications for ON 01910.Na ore being probed, both as a single agent and in combination therapy. An oral formulation of ON 01910.Na is also being tested in patients. |
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