| 产品描述： | COH000 is a covalent and irreversible inhibitor of small ubiquitin-like modifier (SUMO)-activating enzyme and inhibited SUMOylation (IC50: ~ 0.2 μM in vitro) |
| 靶点： |
E1/E2/E3 Enzyme |
| 体外研究： |
COH000 inhibited SUMOylation with an average IC50 of approximately 0.2 μM in vitro but did not inhibit ubiquitylation in a Ubc13-mediated poly-ubiquitylation assay tested under the same condition at concentrations up to 100 μM. COH000 treatment induced apoptosis in HCT-116 cells. The level of apoptosis was reduced when SAE2 was overexpressed by transfection and was increased when SAE2 was knocked down in HCT116 cells. |
| 体内研究： |
Once the tumor became palpable, the tumor-bearing Es1e/SCID mice were treated with COH000 or vehicle for 14 days. COH000 significantly inhibited tumor growth. In addition, COH000 significantly reduced SAE2 levels in tumor tissues. |
| 细胞实验： |
Cell proliferation was measured using a CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS-based) after COH000 or its analog (54 or 55) treatment at the indicated concentrations and the time points. Briefly, cells were incubated with 20 mL of CellTiter 96 AQueous reagentafter the treatment and incubated at 37C until color development. Absorbance measurements were performed using a SpectraMax M5 reader. For assays measuring anti-proliferation effects, all values were normalized to the vehicle treatment. All values are represented graphically as mean ± standard deviation (STDEV) from three independent samples (n=3). |
| 动物实验： |
Mice were housed in a controlled environment (12-h light/12-h dark cycle) with access to waterand fed a standard diet generally from 6 to 8 weeks of age. Body weight was measured weekly and food intake was monitored. For colorectal cancer xenograft with COH000 treatment, HCT116 cells were s.c. injected into a plasma esterase-deficient SCID mouse strain (Es1e/SCID), male, 8-10 weeks. When the tumors became palpable, COH000 was administered subcutaneously peritumoral injection once a day at a dose of 10 mg per kilogram of body weight. Mice in the control group received equal volumes of vehicle (5% DMSO, 30% solutol in PBS). Tumor volume was measured until the endpoint was reached. Mice were euthanized using CO2 inhalation and tumors were excised. |
| 参考文献： |
1. Sun B, Wu H, Lu J, et al. Irisin reduces bone fracture by facilitating osteogenesis and antagonizing TGF-β/Smad signaling in a growing mouse model of osteogenesis imperfecta. Journal of Orthopaedic Translation. 2023, 38: 175-189. |
| 溶解性： |
Soluble in DMSO |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.384 ml |
11.92 ml |
23.84 ml |
| 5 mM |
0.477 ml |
2.384 ml |
4.768 ml |
| 10 mM |
0.238 ml |
1.192 ml |
2.384 ml |
| 50 mM |
0.048 ml |
0.238 ml |
0.477 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京