The evolving tale of immunomodulatory drugs and cereblon

The immunomodulatory drugs (IMiDs), of which thalidomide was the first in class, have had a complex therapeutic history. Although these drugs are now widely used to treat multiple myeloma, the precise molecular mechanism of action of these agents has remained elusive. The finding that IMiDs bind cereblon, with subsequent activation of E3-ubiquitin ligase activity and degradation of the key transcription factors IKZF1 and IKZF3, has provided insight into these drugs but leaves many questions unanswered.