Oral non-peptide STAT6 degrader WW-210 eases atopic dermatitis in mice
- Replaces the earlier phosphopeptide-based STAT6 PROTAC with non-peptide degraders designed for oral dosing.
- WW-210 degraded STAT6 at very low concentrations with a wide selectivity window over other STAT family members.
- It showed measurable oral bioavailability and degraded STAT6 in blood and spleen; in an atopic dermatitis mouse model it eased skin lesions, lowered serum IgE and reduced mast cell infiltration.
💡 Points
STAT6 is a transcription factor with a flat, polar SH2 surface, exactly the kind of target where inhibitors struggle and degraders can sidestep the problem. Getting oral exposure from a PROTAC that started life as a phosphopeptide is the real achievement; I'd like to see how molecular weight and polarity were managed, and whether the STAT-family selectivity holds in primary T cells.