Selective PROTACS against PDE5 + PDE7 as novel treatments for CNS disorders and cancer

摘要：本项目将重点对PDE5和PDE7亚型选择性PROTACs进行检测和优化，以作为治疗中枢神经系统疾病和癌症的新方法。PDE5和PDE7 PROTACs将在细胞系中进行测试，以确定PDE5和PDE7的成功敲除，并确定PROTACs对特定PDE亚型的选择性。分子建模技术将用于可视化protac -靶标相互作用，并告知药物结构优化。此外，生物信息学分析将有助于检测PDE5和PDE7异构体在其他疾病中的失调，这些疾病可能适合PDE5/PDE7 PROTAC药物的开发和治疗。

Studentship strategic priority area: Industrial collaborative researchKeywords: PROTACs, phosphodiesterasesAbstract: This project will focus on testing and optimising PDE5 and PDE7 isoform selective PROTACS that could be used as novel treatments for CNS disorders and cancer. PDE5 and PDE7 PROTACs will be tested in cell lines to determine successful knockdown of PDE5 and PDE7 and establish selectivity of PROTACs towards specific PDE isoforms. Molecular Modelling techniques will be used to visualise PROTAC-target interaction and inform drug structure optimisation. Furthermore, bioinformatic analysis will help detect dysregulation of PDE5 and PDE7 isoforms in other diseases that could be amenable to PDE5/PDE7 PROTAC drug development and treatment.