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Discovery of a Novel Series of iso-Indolinone-Based Glutarimides as Highly Efficacious and Selective IKZF2 Molecular Glue Degraders

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This research finds new glutarimides enhance IKZF2 degradation in Tregs, suggesting potential in cancer immunotherapy.

Compound 55 exhibits over 90% Dmax in Jurkat cells, showcasing its efficacy as an IKZF2 degrader.
Selectivity over IMiD neo-substrates and favorable properties make compound 55 a promising candidate.
PK/PD studies revealed lasting IKZF2 degradation in mouse spleen and thymus post oral administration.
These findings indicate the potential of compound 55 as a basis for future preclinical studies in immunotherapy.

Zhang et al. (2025) studied this question.

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