Discovery of First-in-class WDR5 PROTACs as a Novel Therapeutic Strategy for MLL-rearranged Leukemias

项目摘要 这是一个研究补充申请，以促进健康相关研究的多样性（PA-21-071）。 与本申请相关的父R 01授权的标题为“发现一流的WDR 5 PROTAC 作为MLL重排白血病的一种新的治疗策略”，并得到NCI的支持 （1R01CA268384-01）。Jerrel Catlett是多样性候选人。他是一名非裔美国公民 目前是纽约西奈山伊坎医学院的MD/PhD学生。在这个项目中， 候选人将进行结构生物学，生物化学，生物物理学和计算生物学研究， 表征PRORAC诱导的WDR 5-PROTAC-E3连接酶三元复合物，并提供新的结构 PROTAC诱导的三元复合物形成的见解，并指导设计和开发更多 有效的WDR 5降级器。

Project Summary This is an application for a Research Supplement to Promote Diversity in Health-Related Research (PA-21-071). The parent R01 grant associated with this application is entitled “Discovery of First-in-class WDR5 PROTACs as a Novel Therapeutic Strategy for MLL-rearranged Leukemias” and supported by the NCI (1R01CA268384-01). Jerrel Catlett is the diversity candidate. He is a US citizen of African-American descent and is currently an MD/PhD student at the Icahn School of Medicine at Mount Sinai, New York. In this project, the candidate will conduct structural biology, biochemistry, biophysics and computational biology studies to characterize PRORAC-induced WDR5-PROTAC-E3 ligase ternary complexes, and to provide new structural insights for the PROTAC-induced ternary complex formation and guide design and development of more effective WDR5 degraders.