Research progress on the anticancer mechanism of thalidomide and the function of its target protein CRBN

Thalidomide and its analogues( lenalidomide and pomalidomide) are small glutamic acid derivatives with strong im-munomodulatory effects, belonging to immunomodulatory drug( IMi D) class. In addition,these thalidomide analogues demon-strate an overlapping and diverse range of biological activities,including anti-angiogenesis and anti-teratogenicity. Importantly,the IMi Ds exert anticancer effects such as inhibiting tumor cell proliferation and promoting tumor cell apoptosis and play important roles especially in clinical treatment of multiple myeloma.Recently,the screening and discovery of thalidomide binding protein,CRBN provides new clues to the research of its pharmacological mechanisms and the develop ment of new generation of thalidomide derivatives with less toxic side effects and more antitumor potency. This review briefly discusses the underlying mechanism of thalidomide and their derivatives' action and their new identified target,as well as their contribution to the treatment of multiple myeloma.