Structure-based design of MIF Antagonists

• MIF: Macrophage migration Inhibitory Factor is a pro-inflammatory cytokine
• Clinically Validated Target: anti-MIF antibodies & MIF KO’s have in vivo activity in multiple cancer and inflammatory indications • cancer (e.g., prostate, colon, lung, melanoma) • rheumatoid arthritis, sepsis, atherosclerosis, asthma, and ARDS
• Two Diverse Highly Potent Series by Design (a): • SAR Yield: ~400 compounds, low-nM MIF-binding • ~1000x more potent than others’ antagonists
• Commercial: both series are drug-like with economical synthesis routes
• HitProfiling and CYP450s: clean/excellent metabolic stability
• Biologically Active (b): PC3 prostate cancer cells