Identification and optimisation of small molecule inhibitors of APP1 as novel therapeutics.

这项建议的目的将是确定有效的、可溶的和细胞可渗透的化学工具作为APP的抑制剂，有可能进一步验证其抑制机制，并进一步开发成治疗药物。我们的战略是在计算理性HIT验证练习中利用APP的高分辨率结构来开发有效的和细胞渗透的抑制剂。其目标是产生类似铅的化学探针，可以进一步开发成治疗剂。

The objective of this proposal will be to identify potent, soluble and cell permeable chemical tools as inhibitors of APP with potential to further validate the mechanism of inhibition and for further development into a therapeutic drug. Our strategy is to exploit the high-resolution structure of APP in a computational rational hit validation exercise to develop potent and cell permeable inhibitors. The aim will be to generate lead-like chemical probes that can be further developed into therapeutic agents.