Thalidomide as a multitarget drug and its application as a template for drug design

Thalidomide is a hypnotic/sedative drug which was withdrawn from the market because of teratogenicity. However, it has been established to be useful for the treatment of various diseases, including Hansen's disease and various cancers. Thalidomide elicits a wide range of pharmacological effects, including anticachexia; antitumor-promoting, antiangiogenic, immunosuppressing, antiviral, hypoglycemic, cell differentiation-inducing and antimetastatic activities. It appears to be a multitarget drug, and hypothetical target events/molecules of thalidomide include TNF-alpha production, nuclear androgen receptor, cyclooxygenases, nuclear retinoic acid receptor, aminopeptidases and a-glucosidase. Specific and potent compounds acting on each of these target phenomena/molecules have been prepared by appropriate modification of the thalidomide structure and are expected to be superior lead compounds for novel immunomodulators, antiangiogenic agents and antitumor-promoting agents.