BLIMP-IMiD

BLIMP-IMiD is a first-in-class, dual-targeting small molecule degrader developed by AstraZeneca for the treatment of multiple myeloma. It is designed as a single bifunctional molecule that utilizes the Cereblon (CRBN) E3 ligase to induce the proteasomal degradation of both B lymphocyte-induced maturation protein-1 (BLIMP1) and the traditional immunomodulatory drug (IMiD) neosubstrates, Ikaros (IKZF1) and Aiolos (IKZF3). BLIMP1, encoded by the PRDM1 gene, is a transcriptional corepressor essential for plasma cell differentiation and survival, and has been identified as a top genetic dependency in multiple myeloma. By integrating BLIMP1 degradation with the degradation of IKZF1 and IKZF3, BLIMP-IMiDs overcome the competitive antagonism observed when combining separate BLIMP1 PROTACs with IMiDs, leading to potent anti-proliferative effects and near-complete tumor growth inhibition in preclinical models.