GATA3 molecular glue degrader

GATA3 molecular glue degraders are a novel class of small molecules designed to induce the targeted proteasomal degradation of the transcription factor GATA3, a key functional dependency in ER-positive (luminal) breast cancers. Developed by researchers at Novartis, these compounds function as molecular glues that facilitate the formation of a ternary complex between the DNA binding domain (DBD) of GATA3 and the Cereblon (CRBN) E3 ubiquitin ligase. Because GATA3 lacks traditional small-molecule binding pockets, the degrader targets conserved CxxCG motifs within the DBD. This mechanism leads to the depletion of GATA3 and subsequently disrupts the recruitment of the estrogen receptor (ER) to chromatin, inhibiting tumor growth. Preclinical studies have demonstrated significant efficacy in ER-positive breast cancer models both in vitro and in vivo, and the mechanism appears conserved across other GATA family members.

Other names

Pan-GATA molecular glueGATA3 glue degraderGATA-3 glue degraderGATA 3 glue degrader