Thalidomide (Immunoprin, Contergan and Thalomid)

Description: Thalidomide (trade names Immunoprin, Contergan and Thalomid among others) is a potent immunomodulatory agent and a drug approved in the 1950s.  It is commonly used as the ligand of E3 ligase in PROTACs (proteolysis targeting chimeras), a protein degradation technology. Thalidomide is the prototypic drug of the thalidomide class of drugs that are used primarily for the treatment of certain cancers (e.g. MM-multiple myeloma) and of a complication of leprosy. It was introduced as a sedative drug, immunomodulatory agent in 1950s by the German pharmaceutical company Grunenthal and also is investigated for treating symptoms of many cancers. Nowadays, Thalidomide is often times used as a PROTAC (Proteolysis Targeting Chimera) building block which acts as a ligand for the E3 ubiquitin ligase cereblon. PROTAC is a technology utilizes hetero-bifunctional small molecules whereby one end of the molecule recruits an E3 ubiquitin ligase while the other end engages the target protein. Thalidomide inhibits an E3 ubiquitin ligase, which is a CRBN-DDB1-Cul4A complex. Thalidomide is a potent costimulator of primary human T cells in vitro, synergizing with stimulation via the T cell receptor complex to increase interleukin 2-mediated T cell proliferation and interferon gamma production.