Advances in Research on CELMoDs IKZF_1/3 Degraders

IKZF₁ (Ikaros) and IKZF₃ (Aiolos) are zinc finger transcription factors, which involve a variety of signal pathways and regulatory mechanisms, and are particularly critical to the development of immune cells and the stability of the internal environment. The overexpression of IKZF_1/3 is closely related to the occurrence and development of a variety of hematological malignancies. Immunomodulatory drugs (IMiDs) degrade IKZF_1/3 by interacting with cereblon (CRBN) E3 ligase. In clinical practice, IMiDs in combination with other drugs such as proteasome inhibitors and monoclonal antibodies, are applied for the treatment of multiple myeloma, non-Hodgkin's lymphoma and other cancers. However, the above strategy for recurrent/refractory tumors is not satisfactory, and there is still a huge unmet clinical demand. CRBN E3 ubiquitin ligase modulators (CELMoDs), a new type of novel immunomodulatory drugs, can degrade IKZF_1/3 more effectively and deeply, and show its superiority in in vitro and in vivo trials. Quite a few CELMoDs have entered clinical evaluation. This paper reviews the research progress of CELMoDs IKZF_1/3 degraders in order to provide some reference for the development of anti-hematologic tumor drugs.