Thalidomide #83687

Thalidomide was briefly used as an antiemetic and sedative to treat “morning sickness,” anxiety, and insomnia before being removed from the market due to its association with neonatal mortality and severe birth defects. It reentered the clinical marketplace decades later as an antiangiogenic and anti-inflammatory agent effective against several forms of cancer, leprosy, and some inflammatory disorders (1,2). Thalidomide and its analogs, Lenalidomide and Pomalidomide, are immunomodulatory drugs that bind the CRL4 E3 ubiquitin ligase substrate receptor Cereblon (CRBN) to promote the ubiquitination and targeted degradation of several transcription factors. These compounds target several proteins, including C₂H₂ zinc finger transcription factors Ikaros, Aiolos, and ZFP91, as well as casein kinase 1α, to control a broad transcriptional network (3,4). Thalidomide can also downregulate the zinc finger transcription factor SALL4, which is implicated in some human malformation syndromes, including Duane-radial ray syndrome (Okihiro syndrome) and Acro-renal-ocular syndrome (5).