pyridylbenzylamine analog 1

Pyridylbenzylamine analog 1 is a potent and selective small molecule degrader of IKZF2 (Helios), a zinc finger transcription factor that plays a critical role in maintaining the immunosuppressive phenotype of regulatory T (Treg) cells. Developed by Bristol Myers Squibb as an optimization of the earlier candidate BMS-986449, this compound is a lenalidomide-based molecular glue designed to recruit the cereblon (CRBN) E3 ubiquitin ligase complex. This recruitment leads to the ubiquitination and subsequent proteasomal degradation of Helios. By selectively degrading Helios while exhibiting improved selectivity over related neosubstrates such as IKZF1 (Ikaros), IKZF3 (Aiolos), and CK1α, the drug aims to reprogram Treg cells within the tumor microenvironment to enhance antitumor immunity. Preclinical studies have demonstrated that the compound possesses favorable ADME properties and robust in vivo pharmacodynamic effects in syngeneic mouse models.

Other names

pyridylbenzylamine appended lenalidomide analog