In the current study, we show that the novel thalidomide-like compound F-3,6′-DP effectively ameliorates systemic and brain inflammation, but although it binds to the key protein cereblon, it does not efficiently trigger the degradation of transcription factors (SALL4, Ikaros, and Aiolos) associated with the teratogenic and anti-proliferative responses induced by this drug class, thereby providing a different profile to pomalidomide. Here, IKZF1 is linked to brain inflammatory disease.