Progress in the development of macrophage migration inhibitory factor small-molecule inhibitors

Macrophage migration inhibitory factor (MIF) functions as a critical cytokine regulating inflammatory and immune responses. Extensive research has demonstrated its involvement in the progression of various cancers, autoimmune diseases, and inflammatory disorders, establishing it as a pivotal target for anti-inflammatory and anticancer interventions. Therapeutic strategies aimed at MIF primarily focus on suppressing its activity through small molecule inhibitors and natural compounds. This review synthesizes current knowledge on MIF, encompassing its structural characteristics, enzymatic functions, signaling pathways, and roles in disease pathogenesis. Additionally, it provides an in-depth analysis of recent advancements in MIF inhibitor development, including design methodologies, structure-activity relationships, advanced eutectic analysis techniques, and key experimental findings. The discussion aims to support the development of safer, more effective, and highly selective small molecule inhibitors targeting MIF.