{"title":"Mutations that stick: Unexpected discovery of molecular glue mimicry","authors":"Rory Whelan, Ferran José-Duran, Cristina Mayor-Ruiz","doi":"10.1016/j.molcel.2025.03.017","DOIUrl":null,"url":null,"abstract":"Recent elegant studies in <em>Nature</em><span><span><sup>1</sup></span></span><sup>,</sup><span><span><sup>2</sup></span></span> uncovered an unprecedented molecular glue-like mechanism of action for the preclinical drug UM171. This small molecule showed striking functional and structural similarities to brain cancer mutations that prompt neomorphic protein interactions. This phenomenon of chemical-genetic convergence could be reverse-engineered to aid the rational design of induced proximity therapeutics.","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":"25 1","pages":""},"PeriodicalIF":16.6000,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.molcel.2025.03.017","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Recent elegant studies in Nature1,2 uncovered an unprecedented molecular glue-like mechanism of action for the preclinical drug UM171. This small molecule showed striking functional and structural similarities to brain cancer mutations that prompt neomorphic protein interactions. This phenomenon of chemical-genetic convergence could be reverse-engineered to aid the rational design of induced proximity therapeutics.
期刊介绍：
Molecular Cell is a companion to Cell, the leading journal of biology and the highest-impact journal in the world. Launched in December 1997 and published monthly. Molecular Cell is dedicated to publishing cutting-edge research in molecular biology, focusing on fundamental cellular processes. The journal encompasses a wide range of topics, including DNA replication, recombination, and repair; Chromatin biology and genome organization; Transcription; RNA processing and decay; Non-coding RNA function; Translation; Protein folding, modification, and quality control; Signal transduction pathways; Cell cycle and checkpoints; Cell death; Autophagy; Metabolism.
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