Here, thanks totheir ability to degrade JAK1 and JAK2 (JAPT7 with DC50 of 682 nM (JAK1) and 2.32 μM (JAK2), and JAPT8 of 1.32 μM (JAK1) and 2.36 μM (JAK2)), both compoundsdemonstrated to downregulate AD-related inflammatory cytokines, suchas interleukin (IL)-4, IL-13, IL-33, and thymic stromal lymphopoietin.While most PROTACs exhibit a hook effect at high concentrations, JAPT7 and JAPT8 maintained their activity, evenat higher doses. Here, JAK2 is linked to Alzheimer disease.