ABSTRACT
Thalidomide and its analogues ( lenalidomide and po-malidomide) are small glutamic acid derivatives with strong im- ＜br> munomodulatory effects, belonging to immunomodulatory drug ( IMiD ) class . In addition , these thalidomide analogues demon- ＜br> strate an overlapping and diverse range of biological activities, including anti-angiogenesis and anti-teratogenicity. Importantly, the IMiDs exert anticancer effects such as inhibiting tumor cell proliferation and promoting tumor cell apoptosis and play impor-tant 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 pharma-cological mechanisms and the develop ment of new generation of ＜br> thalidomide derivatives with less toxic side effects and more anti-tumor 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 treat-ment of multiple myeloma.
ABSTRACT
objective To establish a molecular platform for screening thalidomide derivatives with potential high anti-tumor activities. Methods Human cereblon(CRBN) and Ikaros family zinc finger protein 1(IKZF1) cDNA were amplified and cloned into pXJ40-myc and pcDNA3-FLAG vectors respectively. Then the two constructs were transfected into 293T cells and the anti-tumor activities of thalidomide and its derivatives were reflected by their effects on the binding between CRBN and IKZF1 proteins. Results Both CRBN and IKZF1 were successfully expressed in 293T cells. Thalidomide and two of its derivatives were found to enhance the interaction between CRBN and IKZF1 significantly. Conclusion A molecular platform was successfully established for screening thalidomide derivatives with potential high anti-tumor activities and two thalidomide derivatives could potentiate the binding between CRBN and IKZF1, suggesting that they possess potential anti-tumor activities.