生物活性
MSA-2 是一种口服的非核苷酸 STING 激动剂，具有抗肿瘤活性，对人的 STING 亚型 WT 和 HAQ 的 EC50 分别为 8.3 和 24 μM。MSA-2 induces tumor regression with durable antitumor immunity, and synergizes with anti-PD-1 in syngeneic mouse tumor models. 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. In tumor models that are moderately or poorly responsive to PD-1 blockade, combinations of MSA-2 and anti-PD-1 antibody are superior in inhibiting tumor growth and prolonging survival over monotherapy.
化学数据
| 分子量 | 294.32 |
| 分子式 | C14H14O5S |
| CAS号 | 129425-81-6 |
| 纯度 | 98.44% |
| 溶解性（25°C） | DMSO ≥ 40 mg/mL |
| 储存和运输条件 | 2-8°C, protect from light, sealed
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | THP-1 cells, mouse macrophages |
| 方法 | In the primary screen, THP-1 cells are incubated, in 1536-well plates, with test compounds (20 μM) in a RPMI1640-based assay medium in the presence of 5% carbon dioxide at 37°C for 5 hours. IFN-b levels are determined using an AlphaLISA assay and an EnVision Reader and expressed as percentages of IFN-b induced by cGAMP. STING binding activity of compounds is evaluated with a competitive radioligand binding assay using tritiated cGAMP and membrane embedded full-length recombinant human and mouse STING generated in insect cells. STING pathway activation by MSA-2 is assessed by Western blotting, probing phosphorylation status and total protein levels of STING, TBK-1, and IRF3 by using commercially available antibodies. |
| 浓度 | 20 μM, 0.16 μM-100 μM |
| 处理时间 | 5 h |
| 动物实验 |
|---|
| 动物模型 | C57BL/6J mice, NSG mice, BALB/c mice, nude NCr mice |
| 配制 | - |
| 剂量 | 25 mg/kg, 40 mg/kg, 50 mg/kg, 60 mg/kg, 80 mg/kg, 160 mg/kg |
| 给药处理 | intra tumor injection, SC, PO |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.3977 mL | 16.9883 mL | 33.9766 mL |
| 5 mM | 0.6795 mL | 3.3977 mL | 6.7953 mL |
| 10 mM | 0.3398 mL | 1.6988 mL | 3.3977 mL |
