Prohibitin-1（PHB1）及其同系物PHB2是一种支架蛋白，并作为许多信号通路的枢纽。由于PHB对细胞信号的调控作用，它们在癌症的病因、炎症、心血管疾病、神经退行性疾病、糖尿病、肥胖和由几种病原体引起的感染等疾病中起到重要作用。一些作用于PHB的小分子已经确定，而且这些不同种类的PHB配体显示不同的生物反应，表明这类分子可以作为化学探针检测PHB的选择性生物功能。.本项目的目标是开发新的PHB配体作为化学探针探索各种生物功能。我们将合成一系列先导化合物的衍生物来获得构效关系，然后通过骨架迁越技术对先导化合物进行优化，从而找到高效和高选择性的化学探针来破译许多类型细胞中的PHB的功能。这些化学探针将对那些探索PHB功能的细胞生物学家和生理学家非常有用。事实上PHB已逐渐成为细胞生物学中重要的信号转导蛋白。在这一背景下推进PHB配体的发现，将大大加快新兴生物学说假设的验证。

Prohibitin-1 (PHB1) and its homolog PHB2 are scaffold proteins acting as a hub for many signaling pathways. Due to their regulatory action on cell signaling, PHBs are involved in the etiology of cancers, inflammatory, cardiovascular, and neurodegenerative diseases, diabetes mellitus, obesity and infection by several pathogens. Some small molecules that target PHBs have been identified and these different classes of PHB ligands display dissimilar biological responses, indicating that such molecules could be used as chemical probes to examine selective functions of PHBs..The goal of this project is to develop new PHB ligands as chemical probes to explore various functions of PHBs. We will synthesize analogues of our hits to obtain complementary structure-activity relationships (SAR) insight, then hit to lead optimization and scaffold hopping will be performed to identify highly potent and selective chemical probes to decipher the roles of PHBs in many cell types.These chemical probes delivered will be very useful to the community of cell biologists and physiologists to explore the functions of PHBs. Indeed PHBs are emerging as important signaling proteins in cell biology. Advancing the discovery of PHB ligands in this context, will greatly accelerate the testing of emerging biological hypotheses.