msa-2

MSA-2 is an orally available non-nucleotide STING agonist. The non-covalent dimer of MSA-2 binds to STING with nanomolar affinity. It shows anti-tumor activity in syngeneic mouse tumor models, synergizes with anti-PD-1, stimulates tumor secretion of interferon-β, induces tumor regression, and has long-lasting anti-tumor immunity. [3]

MSA-2-Pt is an orally active STING agonist with excellent cell membrane permeability. It can induce cell death via Pt, releasing damaged DNA to activate the cGAS-STING pathway. Additionally, MSA-2-Pt can directly activate the STING pathway through MSA-2. This compound is applicable in cancer research.

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-IN-12 (compound Y2) acts as an inhibitor of STING. It suppresses IFNβ gene expression induced by SR717 with an IC50 of 0.75 μM. Additionally, STING-IN-12 inhibits STING pathway activation induced by the STING agonist SR717 in THP1 cells and by MSA-2 in mice.

STING-IN-8 (Compound 15b) is a potent inhibitor of the stimulator of interferon genes (STING), with an IC50 value of 0.121 μM in humans and 0.033 μM in mice. This compound effectively inhibits STING signaling induced by MSA-2 or 2',3'-cGAMP, as well as the levels of immune and inflammatory cytokines in human and mouse cells. STING-IN-8 shows significant potential for research in STING-related inflammatory and autoimmune diseases.