MSA-2 dimer is a selective, orally active non-nucleotide STING agonist (Kd=145 μM) with long-term antitumor and immunogenic activity. MSA-2 dimer is bound to STING as a non-covalent dimer exhibiting higher permeability than cyclic dinucleotide[1].
MSA-2 dimer (60 mg/kg; p.o.; 50 days) inhibits tumor growth and prolongs overall survival[1]. MSA-2 dimer (40 mg/kg; s.c.; 25 days) induces complete tumor regression[1].MSA-2 dimer (60 mg/kg; p.o.; 4 hours) increases proinflammatory cytokine (IFN-β) level in tumors[1].MSA-2 dimer (60 mg/kg; s.c.; 4 hours) concentrations is observed in tumors than in plasma or other nontumor tissues [1].MSA-2 dimer (THP-1 cells) induces phosphorylation of both TBK1 and IR. MSA-2 dimer (10 μM and 33 μM; macrophages) induces IFN-β[1].MSA-2 dimer also exhibits dose-dependent antitumor activity when administered by IT, SC, or PO routes[1].
[1]. Pan BS, et al. An orally available non-nucleotide STING agonist with antitumor activity. Science. 2020;369(6506):eaba6098.