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

发现一流的 WDR5 PROTAC 作为 MLL 重排白血病的新型治疗策略

基本信息

批准号：
10745902
负责人：
Jian Jin
金额：
$ 9.7万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10745902
关键词：
Affinity African American Antineoplastic Agents Area Binding Biochemistry Biophysics Calorimetry Complex Computational Biology Computer Analysis Data Analyses Development Generations Grant Health Ligands Lysine MLL-rearranged leukemia New York Parents Patients Pharmacology Prognosis Protac Proteins Public Health Reporting Research Resolution Site-Directed Mutagenesis Statistical Data Interpretation Structure System Techniques Titrations Training Translational Research Ubiquitin X-Ray Crystallography design doctoral student drug discovery elongin B elongin C improved insight interest medical schools multicatalytic endopeptidase complex novel therapeutic intervention protein expression protein protein interaction protein purification standard care structural biology training opportunity translational medicine treatment strategy ubiquitin-protein ligase

项目摘要

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.

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。