Dual IKZF2 and CSNK1A degrader for AML

A cereblon-dependent molecular glue degrader that targets both the transcription factor IKZF2 and the kinase CSNK1A could help treat AML by inducing cell cycle arrest, apoptosis and differentiation of leukemic cells.

Structure-guided design and cell-based screening of a library of Revlimid lenalidomide derivatives identified a compound that degraded IKZF2, with limited degradation of the Revlimid targets IKZF1 and IKZF3, and inhibited the growth of a panel of eight AML cell lines with IC50s from single-digit nanomolar to low micromolar concentrations; subsequent proteomic studies showed the compound also degraded CSNK1A. ...