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

S.克纳普和他的团队将继续致力于提供化学探针来询问SCLC肿瘤发生的关键途径。特别是，他们将使他们越来越多的化学探针的集合靶向表观遗传修饰剂和激酶的机制研究在SCLC可用。此外，他们将继续分析SCLC细胞系的化学筛选，以确定这些脆弱性。在干扰SCLC关键途径的新努力中，他们将努力创造新的分子，以基于结构的药物设计方法抑制端粒酶的催化活性，利用人类端粒酶的晶体学和EM研究的新见解。最后，该团队将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，如与Michael Hölzel团队合作的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.