NIBR’s IKZF2 molecular glue degrader; plus new optimized base editors and more

Novartis Institutes for BioMedical Research (NIBR) researchers described in Cell Chemical Biology a selective molecular glue degrader designed to target the Treg-promoting zinc finger transcription factor IKZF2, while sparing the classical imid targets IKZF1/3, by redirecting the degradation selectivity of an E3 ubiquitin ligase binder from IKZF1 toward IKZF2.

The IKZF2 degrader, dubbed NVP-DKY709, delayed tumor growth in mice with humanized immune systems, enhanced immunization responses in cynomolgus monkeys, and decreased the suppressive activity of human Tregs, rescuing cytokine production by exhausted T effector cells in co-cultures. ...