Proteolysis Targeting Chimera (PROTAC) for Macrophage Migration Inhibitory Factor (MIF) Has Anti‐Proliferative Activity in Lung Cancer Cells

Macrophage migration inhibitory factor (MIF) is involved in protein-protein interactions that play key roles inflammation and cancer. Current strategies to develop small molecule modulators of MIF functions are mainly restricted the tautomerase active site. Here, we use this site proteolysis targeting chimera (PROTAC) order eliminate from its interaction network. We report first potent MIF-directed PROTAC, denoted MD13, which induced almost complete degradation at low micromolar concentrations with a DC50 around 100 nM A549 cells. MD13 suppresses proliferation cells, can be explained by deactivation MAPK pathway subsequent induction cell cycle arrest G2/M phase. also exhibits antiproliferative effect 3D tumor spheroid model. In conclusion, describe PROTAC (MD13) as research tool, demonstrates potential PROTACs cancer therapy.