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

克纳普和他的团队将继续致力于提供化学探针，以询问小细胞肺癌肿瘤发生的关键途径。特别是，他们将使他们越来越多的针对表观遗传修饰物和激酶的化学探针集合，用于SCLC的机制研究。此外，他们将继续对小细胞肺癌细胞系进行基于化学物质的筛选分析，以确定这种脆弱性。在干扰小细胞肺癌关键通路的新努力中，他们将努力创造新的分子来抑制端粒酶的催化活性，这是一种基于结构的药物设计方法，利用人类端粒酶的结晶学和EM研究的新见解。最后，该团队将与Michael Hölzel的团队合作，继续开发化学降解剂，用于定向降解小细胞肺癌生物学中涉及的关键蛋白质，包括赖氨酸甲基转移酶，如G9a。

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.