Unveiling New Triazoloquinoxaline-Based PROTACs Designed for the Selective Degradation of the ncBAF Chromatin Remodeling Subunit BRD9.

ABSTRACT: PROteolysis Targeting Chimera (PROTAC) technology is an innovative and potent approach for achieving targeted protein degradation (TPD). Within bromodomain-containing proteins, various degraders targeting BET family-related targets, for example, BRD4, were developed in the last years. On the other hand, a limited number of PROTACs acting against non-BET proteins were reported so far. Among them, BRD9 was recently linked to oncogenic roles in the tumorigenesis processes, especially in sarcomas and leukemias. Herein, we describe the design and synthesis of a focused collection of new BRD9-targeting degraders based on the [1,2,4]triazolo[4,3-a]quinoxaline heterocyclic scaffold employing two distinct E3 ubiquitin ligase ligands. Through in silico evaluation, synthesis, binding affinity determi

SUBMITTER: Pierri M 

PROVIDER: S-EPMC12172596 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature