Fostriecin and Related Protein Phosphatase Inhibitors

磷霉素和相关蛋白磷酸酶抑制剂

• 批准号: 6620285
• 负责人: DALE L BOGER
• 金额: $ 37.09万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-14 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620285
• 关键词: DNA gyrase; analog; antineoplastics; chemical synthesis; drug design /synthesis /production; enzyme activity; folate; phosphatase inhibitor; phosphoprotein phosphatase; stereochemistry; transport proteins

DESCRIPTION (provided by applicant): A detailed study of fostriecin, a potent and efficacious antitumor agent that inhibits the mitotic entry checkpoint through the selective inhibition of protein phosphatases 2A and 4, and related naturally-occurring and synthetic inhibitors of protein phosphatases (PP) will be conducted. This will include the implementation of an improved second-generation total synthesis of fostriecin, the total synthesis and stereochemical assignment of cytostatin, and the total synthesis and stereochemical assignment of sultriecin. Extensions of the studies to the definition of the fostriecin pharmacophore responsible for its potent and selective PP inhibition and the preparation of more stable and structurally simpler analogues that address issues currently limiting the clinical potential of fostriecin will be pursued.

描述（由申请人提供）：一项关于Fostriecin的详细研究， 和抑制有丝分裂进入检查点的有效抗肿瘤剂 通过选择性抑制蛋白磷酸酶2A和4，以及相关的 蛋白磷酸酶（PP）的天然存在的和合成的抑制剂将 进行。这将包括实施一项改进的 第二代全合成福曲星， 细胞抑制素的立体化学归属，以及全合成和 硫酸菌素的立体化学归属。将研究扩展到 负责其有效性的Fostriecin药效团的定义， 选择性PP抑制剂的制备和结构更稳定 解决目前限制临床潜力的问题的更简单的类似物 将继续使用福司曲菌素。