Targeting key drivers in SCLC for the development of new therapeutic concepts (A07*)

针对 SCLC 的关键驱动因素，开发新的治疗概念 (A07*)

• 批准号: 524421981
• 金额: --
• 依托单位: Institut für Pharmazeutische Chemie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/524421981?language=en
• 关键词: Targeting; key; drivers; SCLC; development

S. Knapp and his team will continue to work on providing chemical probes to interrogate critical pathways of SCLC tumorigenesis. In particular, they will make their growing collections of chemical probes targeting epigenetic modifiers and kinases for mechanistic studies in SCLC available. Furthermore, they will continue their analysis of chemical-based screening of SCLC cell lines to identify such vulnerabilities. In a new effort to interfere with critical pathways in SCLC, they will strive to create novel molecules to inhibit the catalytic activity of telomerase in a structure-based drug design approach exploiting novel insights from crystallography and EM studies of human telomerase. Finally, the team will continue their efforts on developing chemical degraders for targeted degradation of key proteins involved in SCLC biology including lysine methyl transferases such as G9A in collaboration with Michael Hölzel's group.

S. Knapp 和他的团队将继续致力于提供化学探针来探究 SCLC 肿瘤发生的关键途径。特别是，他们将提供越来越多的针对表观遗传修饰剂和激酶的化学​​探针，用于 SCLC 的机制研究。此外，他们将继续对 SCLC 细胞系进行基于化学的筛选分析，以识别此类漏洞。在干扰 SCLC 关键通路的新努力中，他们将利用人类端粒酶晶体学和 EM 研究的新见解，在基于结构的药物设计方法中努力创造新的分子来抑制端粒酶的催化活性。最后，该团队将与 Michael Hölzel 团队合作，继续努力开发化学降解剂，用于靶向降解 SCLC 生物学中涉及的关键蛋白质，包括赖氨酸甲基转移酶（如 G9A）。