3-Aminophthalic acid, a new cereblon ligand for targeted protein degradation by O’PROTAC
Yuqian Yan, Jingwei Shao, Donglin Ding, Yunqian Pan, Phuc Tran, Wei Yan, Zhenyu Wang, Hongyu Li, Haojie Huang
Abstract
In this study, we identified 3-aminophthalic acid as a new ligand of cereblon (CRBN) E3 ubiquitin ligase and developed a phthalic acid-based O'PROTAC for degradation of the ERG transcription factor. This phthalic acid-based O'PROTAC presented an efficacy in degrading ERG comparable to those displayed by pomalidomide-based ERG O'PROTACs. Moreover, phthalic acid-being more chemically stable and economical than classical immunomodulatory drugs (IMiDs)-represents, as a ligand, a new alternative for the development of PROTACs, especially O'PROTACs.
Topics & Concepts
CereblonPhthalic acidUbiquitin ligaseChemistryLigand (biochemistry)UbiquitinDegradation (telecommunications)Protein degradationBiochemistryOrganic chemistryComputer scienceReceptorTelecommunicationsGeneProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysMultiple Myeloma Research and Treatments