Development of IWP-related compounds as selective wt/mutCK1d/e inhibitors, characterization in vitro and in vivo in animal models for their use in new anticancer concepts

开发 IWP 相关化合物作为选择性 wt/mutCK1d/e 抑制剂，在动物模型中进行体外和体内表征，以用于新的抗癌概念

• 批准号: 420839669
• 负责人: Professor Dr. Uwe Knippschild
• 金额: --
• 依托单位: Zentrum für Chirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/420839669?language=en
• 关键词: Development; IWP; related; compounds; selective

The aims of the present application are development and optimization of novel Casein Kinase 1 (CK1) d/e isoform/mutant-specific inhibitors, and their biological characterization in vitro, including tumor cultures, and in vivo using animal models. CK1 isoforms are known for being key regulators of diverse cellular processes. Alterations in the activity and expression of CK1d/e isoforms are linked to the development of several diseases, including neurodegenerative disorders and cancer. This evidence makes CK1isoforms attractive and promising therapeutic drug targets. The discovery and analysis of novel treatments, including active small molecule inhibitors, is of fundamental importance for cancer research and could be integrated into innovative cancer therapy concepts. Potential new compounds could prove beneficial in the case of aggressive tumor entities with high resistance to chemo/radiotherapy and high mutational rates, like triple negative breast cancer, where the reduced effectiveness of conventional treatments is responsible for high mortality rates. We expect to identify novel small molecule inhibitors with therapeutic potential which could contribute to a significant improvement in current treatment concepts for aggressive tumor entities.

本应用的目的是开发和优化新型酪蛋白激酶1(Casein Kinase 1，CK1)D/e异构体/突变特异性抑制剂，以及它们在体外(包括肿瘤培养)和体内动物模型中的生物学特性。众所周知，CK1亚型是多种细胞过程的关键调节因子。CK1d/e亚型活性和表达的改变与几种疾病的发展有关，包括神经退行性疾病和癌症。这一证据使CK1亚型成为具有吸引力和前景的治疗药物靶点。发现和分析新的治疗方法，包括活性小分子抑制剂，对癌症研究至关重要，并可以整合到创新的癌症治疗概念中。潜在的新化合物可能被证明对侵袭性肿瘤实体有利，这些实体对化疗/放射治疗具有高抵抗力和高突变率，如三阴性乳腺癌，传统治疗的有效性降低是导致高死亡率的原因。我们希望找到具有治疗潜力的新的小分子抑制剂，这可能有助于显着改善目前对侵袭性肿瘤实体的治疗概念。