SMARCA2 PROTAC for SMARCA4-mutant lung cancer

A proteolytic targeting chimera (PROTAC) that selectively degrades SMARCA2 — a SWI/SNF chromatin remodeling subunit that promotes chromatin accessibility at the enhancer regions of cell proliferation genes — could help treat SMARCA4-mutant lung via synthetic lethality.

In a panel of SMARCA4-mutant human lung cancer cell lines, A SMARCA2 PROTAC synthesized by conjugating a SMARCA2 bromodomain ligand to the generic E3 ligase ligand pomalidomide via a chemical linker, degraded SMARCA2 protein in a dose- and time-dependent manner, with a median DC50 of 30 nM and an IC50 of 0.11 µM. ...