SBIR 2009 TOPIC 255- TITLE: PYRIDINOPYRIMIDE ANALOGS

SBIR 2009 主题 255-标题：吡啶并嘧啶类似物

• 批准号: 7946605
• 负责人: WEIBO WANG
• 金额: $ 15.24万
• 依托单位: LEO THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7946605
• 关键词: SBIR; 2009; TOPIC; 255; TITLE

B-Raf kinase, a central component of the MAPK signaling pathway, was implicated in many types of malignant cancers including melanomas and thyroid cancers. Accumulating preclinical and clinical studies have suggested an unique opportunity for therapeutic interference by blocking the kinase activity of B-Raf. In this proposal, a set of pyridinopyrimidine analogs were designed as potential B-Raf inhibitors to treat cancers. The design was based on the understanding and insights derived from the analysis of the signature binding motif of this scaffold to protein kinases. The proprietary pyridinopyrimidine scaffold used in the design has demonstrated favorable kinase selectivity profiles, pharmacokinetic and drug properties. The proposed analogs will be synthesized and tested against B-Raf kinases and cancer cell lines. Desirable compounds will be moved quickly to preclinical and clinical studies.

B-Raf 激酶是 MAPK 信号通路的核心组成部分，与多种类型的恶性肿瘤有关，包括黑色素瘤和甲状腺癌。不断积累的临床前和临床研究表明，通过阻断 B-Raf 的激酶活性来进行治疗干预是一个独特的机会。在该提案中，设计了一组吡啶并嘧啶类似物作为潜在的 B-Raf 抑制剂来治疗癌症。该设计基于对该支架与蛋白激酶的特征结合基序的分析所得出的理解和见解。该设计中使用的专有吡啶并嘧啶支架已表现出良好的激酶选择性特征、药代动力学和药物特性。所提出的类似物将被合成并针对 B-Raf 激酶和癌细胞系进行测试。所需的化合物将迅速进入临床前和临床研究。