通过对TPL的化学修饰、结构优化构建高效低毒的靶向STI571抵抗性Bcr-Abl、c-KIT酪氨酸激酶的小分子抑制物
基本信息
结项摘要
蛋白酪氨酸激酶是重要的信号转导分子，在肿瘤发生发展过程中起重要作用。Bcr-Abl融合蛋白形成和c-KIT点突变可以引起肿瘤发生。针对Bcr-Abl和c-KIT的第一代靶向药物STI571治疗相关肿瘤CML、GIST获得了巨大成功。但随着临床上的广泛应用，病人对STI571的耐药日益突显。研制和筛选新型的有自主知识产权的、能有效杀伤STI571抵抗性Bcr-Abl和c-KIT点突变携带细胞的小分子化合物具有战略意义。本课题在已知小分子天然产物TPL可降低STI571抵抗性点突变Bcr-Abl和c-KIT的蛋白表达的基础上，将对TPL进行旨在保效减毒的化学修饰，获取系列衍生物；从TPL衍生物中筛选出对STI571抵抗性点突变Bcr-Abl和c-KIT有抑制作用而毒性比母体化合物降低的候选药物先导化合物，进而对其进行结构优化，以期找到有临床应用前景能克服STI571抵抗性的创新药物。
项目摘要
项目成果
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数据更新时间：2023-05-31
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