msa-2

MSA-2 是可口服的非核苷酸 STING 激动剂，MSA-2 的非共价体系二聚体与 STING 纳摩尔亲和力结合。它在同基因小鼠肿瘤模型中显示抗肿瘤活性，与抗 PD-1 协同作用，可刺激肿瘤分泌干扰素-β，诱导肿瘤消退，具有持久的抗肿瘤免疫。[3]

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.

MSA-2-Pt 是一种具有口服活性的 STING 激动剂，展现出优秀的细胞膜渗透能力。它能够通过 Pt 诱导细胞死亡，释放受损的 DNA，激活 cGAS-STING 通路。同时，MSA-2-Pt 也可以通过 MSA-2 直接刺激 STING 通路。MSA-2-Pt 可用于癌症研究。

STING-IN-12（compound Y2）是一种STING抑制剂。它能够抑制由SR717诱导的IFNβ基因表达（IC50=0.75 μM），并且可以阻断STING激动剂SR717在THP1细胞中引起的STING通路激活，还能够抑制MSA-2在小鼠体内诱导的STING通路激活。

STING-IN-8 (Compound 15b) 是一种高效的干扰素基因刺激因子 (STING) 抑制剂，对人类和小鼠的IC50值分别为0.121 μM和0.033 μM。该化合物能够抑制 MSA-2 或 2’, 3’-cGAMP 引发的 STING 信号传导以及在人体和小鼠细胞中免疫炎症细胞因子的表达。在STING相关的炎症和自身免疫性疾病研究中，STING-IN-8 展现出广阔的前景。