FBXO22 emerges as a new E3 ligase option for protein degraders
- Review of FBXO22, an emerging E3 ubiquitin ligase being explored as an alternative to the heavily used CRBN and VHL for targeted protein degradation.
- Covers the ligase's native biological roles and the degrader chemistry developed so far to redirect its ubiquitination activity toward chosen targets.
- Because FBXO22 is overexpressed in several cancers, it may enable selective degradation in tumor cells.
💡 Points Based on the abstract
Tumor overexpression is a hypothesis, not yet a therapeutic window: matched normal-tissue expression and a ligase-knockout control would be needed before selectivity counts as shown. For a PROTAC program, the practical test is a head-to-head against CRBN and VHL on ternary-complex cooperativity and degradation rate with one target warhead, plus a look at what chemistry current recruiters use and how clean they are proteome-wide.
FBXO22 is a promising E3 ubiquitin ligase for targeted protein degradation ↗