MSA-2
目录号 : GC61092MSA-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。
Sample solution is provided at 25 µL, 10mM.
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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.
| Cas No. | 129425-81-6 | SDF | |
| Canonical SMILES | O=C(C1=CC(C(S1)=C2)=CC(OC)=C2OC)CCC(O)=O | ||
| 分子式 | C14H14O5S | 分子量 | 294.32 |
| 溶解度 | DMSO: 125 mg/mL (424.71 mM) | 储存条件 | 4°C, protect from light |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % ddH2O | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
An orally available non-nucleotide STING agonist with antitumor activity
Science2020 Aug 21;369(6506):eaba6098.PMID: 32820094DOI: 10.1126/science.aba6098
Pharmacological activation of the STING (stimulator of interferon genes)-controlled innate immune pathway is a promising therapeutic strategy for cancer. Here we report the identification of MSA-2, an orally available non-nucleotide human STING agonist. In syngeneic mouse tumor models, subcutaneous and oral MSA-2 regimens were well tolerated and stimulated interferon-β secretion in tumors, induced tumor regression with durable antitumor immunity, and synergized with anti-PD-1 therapy. Experimental and theoretical analyses showed that MSA-2 exists as interconverting monomers and dimers in solution, but only dimers bind and activate STING. This model was validated by using synthetic covalent MSA-2 dimers, which were potent agonists. Cellular potency of MSA-2 increased upon extracellular acidification, which mimics the tumor microenvironment. These properties appear to underpin the favorable activity and tolerability profiles of effective systemic administration of MSA-2.
Genetic polymorphism of Babesia bovis merozoite surface antigens-2 (MSA-2) isolates from bovine blood and Rhipicephalus annulatus ticks in Israel
Vet Parasitol2014 Sep 15;205(1-2):20-7.PMID: 25149097DOI: 10.1016/j.vetpar.2014.07.016
This study demonstrated the genetic diversity among MSA-2c, MSA-2a1 and MSA-2b proteins of Babesia bovis isolates obtained from bovine blood and Rhipicephalus annulatus tick samples. The least identities that were observed among the deduced amino acid sequences of MSA-2c, MSA-2a1 and MSA-2b were 55, 63, and 71%, respectively. During the study four B. bovis calves, aged about 1 month, were found to be infected with virulent field strains and developed babesiosis. Probably, the calves had received insufficient antibodies, or the antibodies raised against the vaccine strain did not cross-protect against virulent field isolates. The complete msa-2 locus from the Israeli B. bovis vaccine strain and two field isolates were characterized. Similarly to the Australian strains and isolates, the msa-2 loci of the examined Israeli strain and isolates had only two msa-2 genes - msa-2c and msa-2a/b - located between msa-2c and orfB. Several of the examined samples, contained different MSA-2 genotypes concurrently. No obvious geographical relationships among isolates from various regions of Israel were established. Moreover, in the phylogenetic analyses, the Israeli deduced MSA-2 amino acid sequences of the three examined genes were clustered together with sequences derived from other countries, proving that the msa-2 gene sequences of B. bovis shared the same genetic characters worldwide. The present study clearly showed that the MSA-2 proteins of B. bovis isolates from Israel were genetically distinct from the vaccine strains. Thus, further research will be needed in order to understand the genetic diversity mechanisms of B. bovis, and the immunological responses of the infected animals.