MS117
目录号 : GC61091
MS117是首创的、具有细胞活性的、不可逆的蛋白精氨酸甲基转移酶(PRMT6)的共价抑制剂，其IC50值为18nM。
Cas No.:2702280-86-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
MS117 is a first-in-class and cell-active irreversible protein arginine methyltransferase 6 (PRMT6) covalent inhibitor, with an IC50 of 18 nM[1].
MS117 (Compound 4) inhibits the PRMT6 methyltransferase activity in a time-dependent manner[1].MS117 (Compound 4) shows moderate selectivity (6-fold) for PRMT6 over PRMT1 (IC50 = 0.1 ± 0.025 µM) and PRMT8 (IC50 = 0.11 ± 0.01 µM) [1].
[1]. Yudao Shen, et al. Discovery of a First-in-Class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor. J Med Chem. 2020 May 28;63(10):5477-5487.
| Cas No. | 2702280-86-0 | SDF | |
| Canonical SMILES | NCCN(C)CC1=CNC=C1C2=CC=CC(NC(C=C)=O)=C2 | ||
| 分子式 | C17H22N4O | 分子量 | 298.38 |
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3514 mL | 16.7572 mL | 33.5143 mL |
| 5 mM | 0.6703 mL | 3.3514 mL | 6.7029 mL |
| 10 mM | 0.3351 mL | 1.6757 mL | 3.3514 mL |
| 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 % saline | ||||||||||
| 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 saline，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。
Discovery of a First-in-Class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor
J Med Chem 2020 May 28;63(10):5477-5487.PMID:32367723DOI:10.1021/acs.jmedchem.0c00406.
Protein arginine methyltransferase 6 (PRMT6) plays important roles in several biological processes associated with multiple cancers. Well-characterized potent, selective, and cell-active PRMT6 inhibitors are invaluable tools for testing biological and therapeutic hypotheses. Although there are several known reversible PRMT6 inhibitors, covalent PRMT6 inhibitors have not been reported. Based on a cocrystal structure of PRMT6-MS023 (a type I PRMT inhibitor), we discovered the first potent and cell-active irreversible PRMT6 inhibitor, 4 (MS117). The covalent binding mode of compound 4 to PRMT6 was confirmed by mass spectrometry and kinetic studies and by a cocrystal structure. Compound 4 did not covalently modify other closely related PRMTs, potently inhibited PRMT6 in cells, and was selective for PRMT6 over other methyltransferases. We also developed two structurally similar control compounds, 5 (MS167) and 7 (MS168). We provide these valuable chemical tools to the scientific community for further studying PRMT6 physiological and pathophysiological functions.
Complementation of an Enterococcus hirae (Streptococcus faecalis) mutant in the alpha subunit of the H(+)-ATPase by cloned genes from the same and different species
Mol Microbiol 1993 Jul;9(1):111-8.PMID:8412656DOI:10.1111/j.1365-2958.1993.tb01673.x.
We isolated an Enterococcus hirae (formerly Streptococcus faecalis) mutant, designated MS117, in which 'G' at position 301 of the alpha-subunit gene of the F1F0 type of H(+)-ATPase was deleted. MS117 had low H(+)-ATPase activity, was deficient in the regulatory system of cytoplasmic pH, and was unable to grow at pH 6.0. When the alpha-subunit gene of E. hirae H(+)-ATPase was ligated with the shuttle vector pHY300PLK at the downstream region of the tet gene of the vector, it was expressed without its own promoter in MS117, and the mutation of MS117 was complemented; the mutant harbouring the plasmid had the ability to maintain a neutral cytoplasm and grew at pH 6.0. We next transformed MS117 with pHY300PLK containing the alpha-subunit gene of Bacillus megaterium F1F0-ATPase constructed in the same way. The transformant grew at pH 6.0, and the ATP hydrolysis activity was recovered. These results suggested that an active hybrid H(+)-ATPase containing the B. megaterium alpha subunit was produced, and that the hybrid enzyme regulated the enterococcal cytoplasmic pH, although the function of the B. megaterium enzyme did not include pH regulation. Thus, our present results support the previous proposal that the enterococcal cytoplasmic pH is regulated by the F1F0 type of H(+)-ATPase.