NEK7 degrader-3 is an orally active and brain-penetrant NEK7 molecular glue degrader with a DC50 of 33.1 nM. NEK7 degrader-3 mediates interaction between NEK7 and E3 ligase cereblon, promoting proteasomal degradation of NEK7 and attenuating NLRP3 inflammasome-mediated inflammatory responses. NEK7 degrader-3 inhibits caspase-1 activity, cytokine release of IL-1β, IL-1α, and IL-18, and pyroptosis -related plasma membrane permeabilization. NEK7 degrader-3 shows antiinflammatory activity in an LPS -induced neuroinflammation mouse model. NEK7 degrader-3 can be used for the research of neuroinflammation [1].
In Vivo, NEK7 degrader-3 (Compound 322) (30 mg/kg; p.o.; bid for 5 days) induces NEK7 degradation and inhibits the production of IL‑1β and IL‑6 in brain tissues of mice with LPS ‑induced neuroinflammation[1].
In Vitro, NEK7 degrader-3 (Compound 322) (0.00001-10 μM) inhibits Caspase‑1 activity and suppresses the release of IL‑1β, IL‑1α and IL‑18 in human monocyte‑derived macrophages and microglia, and inhibits pyroptotic membrane permeabilization[1].
References:
[1]. LIARDO Elisa, et al. TARGETED PROTEIN DEGRADATION. WO2026052637. 2026-3-12
In Vivo, NEK7 degrader-3 (Compound 322) (30 mg/kg; p.o.; bid for 5 days) induces NEK7 degradation and inhibits the production of IL‑1β and IL‑6 in brain tissues of mice with LPS ‑induced neuroinflammation[1].
In Vitro, NEK7 degrader-3 (Compound 322) (0.00001-10 μM) inhibits Caspase‑1 activity and suppresses the release of IL‑1β, IL‑1α and IL‑18 in human monocyte‑derived macrophages and microglia, and inhibits pyroptotic membrane permeabilization[1].
References:
[1]. LIARDO Elisa, et al. TARGETED PROTEIN DEGRADATION. WO2026052637. 2026-3-12