MSA-2 dimer, a selective and orally active non-nucleotide STING agonist with a dissociation constant (Kd) of 145 μM, demonstrates prolonged antitumor and immunogenic activity. It non-covalently binds to STING as a dimer, showing greater permeability compared to cyclic dinucleotide[1].

STING:145 μM (Kd)

MSA-2 dimer exhibits antitumor activity, demonstrating tumor growth inhibition and prolonged overall survival at 60 mg/kg (p.o., 50 days), complete tumor regression at 40 mg/kg (s.c., 25 days), and increased proinflammatory cytokine (IFN-β) levels at 60 mg/kg (p.o., 4 hours) in tumors. Higher concentrations are observed in tumors than in plasma or other non-tumor tissues at 60 mg/kg (s.c., 4 hours). In THP-1 cells, MSA-2 dimer induces the phosphorylation of TBK1 and IR, and in macrophages, it induces IFN-β at 10 μM and 33 μM. Furthermore, MSA-2 dimer exhibits dose-dependent antitumor activity via IT, SC, or PO administration routes[1].