MSA-2是一种口服非核苷酸STING激动剂，对人的STING亚型WT和HAQ的EC50分别为8.3和24μM。MSA-2在同基因小鼠肿瘤模型中显示抗肿瘤活性，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，并与抗PD-1协同作用。
MSA-2, a potent and orally available non-nucleotide STING agonist, has EC50s of 8.3 and 24 μM for human STING isoforms WT and HAQ, respectively. MSA-2 shows antitumor activity and stimulates interferon-β secretion in tumors, induces tumor regression with durable antitumor immunity, and synergizes with anti-PD-1 in syngeneic mouse tumor models[1].
MSA-2 dosed via either PO or SC regimens achieved comparable exposure in both tumor and plasma. MSA-2 also exhibits dose-dependent antitumor activity when administered by IT, SC, or PO routes, and dosing regimens were identified that induced complete tumor regressions in 80 to 100% of treated animals[1].MSA-2 (PO: 60 mg/kg or SC: 50 mg/kg; single dose) that effectively inhibits tumor growth induced substantial elevations of IFN-β, interleukin-6 (IL-6), and TNF-α in tumor[1]. Animal Model: MC38 tumor-bearing C57BL6 mice[1]
MSA-2 是一种有效的口服非核苷酸 STING 激动剂，对人类 STING 亚型 WT 和 HAQ 的 EC50 分别为 8.3 和 24 μM。 MSA-2 显示出抗肿瘤活性并刺激肿瘤中的干扰素-β 分泌，诱导肿瘤消退并具有持久的抗肿瘤免疫力，并在同系小鼠肿瘤模型中与抗 PD-1 药物产生协同作用[1]。
通过 PO 或 SC 方案给药的 MSA-2 在肿瘤和血浆中的暴露量相当。当通过 IT、SC 或 PO 途径给药时，MSA-2 还表现出剂量依赖性抗肿瘤活性，并且确定了给药方案可在 80% 至 100% 的治疗动物中诱导肿瘤完全消退 [1]。MSA-2（PO:60 mg/kg 或 SC:50 mg/kg；单剂量）可有效抑制肿瘤生长，诱导肿瘤中 IFN-β、白介素-6 (IL-6) 和 TNF-α 显着升高[1]。动物模型:MC38荷瘤C57BL6小鼠[1]
[1]. Pan BS, et al. An orally available non-nucleotide STING agonist with antitumor activity. Science. 2020;369(6506):eaba6098.
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