SS-208
目录号 : GC46226
An HDAC6 inhibitor
Cas No.:2245942-72-5
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
SS-208 is an inhibitor of histone deacetylase 6 (HDAC6; IC50 = 12 nM).1 It is selective for HDAC6 over HDAC1, -4, -5, -7, -8, -9, and -11 (IC50s = 1.39, 19.5, 6.91, 8.34, 1.23, 38.2, and 5.12 μM, respectively). SS-208 (0.1-25 μM) inhibits HDAC6 in, but does not induce cell death of, human PC3 prostate, 5637 and T24 bladder, and murine SM1 melanoma cells in vitro. It decreases protein levels of programmed death ligand 1 (PD-L1) in SM1 cells when used at a concentration of 5 μM. SS-208 (25 mg/kg, i.p.) reduces tumor growth and increases the number of intratumoral CD8+, CD4+, and natural killer (NK) T cells in an SM1 murine melanoma model.
|1. Shen, S., Hadley, M., Ustinova, K., et al. Discovery of a new isoxazole-3-hydroxamate-based histone deacetylase 6 inhibitor SS-208 with antitumor activity in syngeneic melanoma mouse models. J. Med. Chem. 62(18), 8557-8577 (2019).
| Cas No. | 2245942-72-5 | SDF | |
| Canonical SMILES | ClC1=C(Cl)C=C(C(NCCC2=CC(C(NO)=O)=NO2)=O)C=C1 | ||
| 分子式 | C13H11Cl2N3O4 | 分子量 | 344.2 |
| 溶解度 | DMF: 1mg/mL,DMSO: 1mg/mL,Ethanol: 30mg/mL,Ethanol:PBS (pH 7.2) (1:2): 0.3mg/mL | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| 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 | 2.9053 mL | 14.5264 mL | 29.0529 mL |
| 5 mM | 0.5811 mL | 2.9053 mL | 5.8106 mL |
| 10 mM | 0.2905 mL | 1.4526 mL | 2.9053 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 New Isoxazole-3-hydroxamate-Based Histone Deacetylase 6 Inhibitor SS-208 with Antitumor Activity in Syngeneic Melanoma Mouse Models
J Med Chem 2019 Sep 26;62(18):8557-8577.PMID:31414801DOI:10.1021/acs.jmedchem.9b00946
Isoxazole is a five-membered heterocycle that is widely used in drug discovery endeavors. Here, we report the design, synthesis, and structural and biological characterization of SS-208, a novel HDAC6-selective inhibitor containing the isoxazole-3-hydroxamate moiety as a zinc-binding group as well as a hydrophobic linker. A crystal structure of the Danio rerio HDAC6/SS-208 complex reveals a bidentate coordination of the active-site zinc ion that differs from the preferred monodentate coordination observed for HDAC6 complexes with phenylhydroxamate-based inhibitors. While SS-208 has minimal effects on the viability of murine SM1 melanoma cells in vitro, it significantly reduced in vivo tumor growth in a murine SM1 syngeneic melanoma mouse model. These findings suggest that the antitumor activity of SS-208 is mainly mediated by immune-related antitumor activity as evidenced by the increased infiltration of CD8+ and NK+ T cells and the enhanced ratio of M1 and M2 macrophages in the tumor microenvironment.