| 产品描述： | SIK抑制剂;SIK Inhibitors;;InformationYKL-05-099 YKL-05-099 is an inhibitor of salt-inducible kinase (SIK) with IC50 of ~10 nM, ~40 nM and ~30 nM for SIK1, SIK2 and SIK3, respectively.TargetsSIK1 (Cell-free assay); SIK3 (Cell-free assay); SIK2 (Cell-free assay) 10 nM; 30 nM; 40 nMIn vitroYKL-05-099 displays cell-based activities consistent with SIK inhibition. Pre-treatment with the indicated concentrations of YKL-05-099 for 24 hr potentiates IL-10 production by Zymosan A-stimulated BMDCs.In vivoWell-tolerated doses of YKL-05-099 achieve free serum concentrations above its IC50 for SIK2 inhibition for > 16 hours and reduce phosphorylation of a known SIK substrate in vivo. While in vivo active doses of YKL-05-099 recapitulate the effects of SIK inhibition on inflammatory cytokine responses, they do not induce metabolic abnormalities observed in Sik2 knockout mice. These results identify YKL-05-099 as a useful probe to investigate SIK function and further support the development of SIK inhibitors for treatment of inflammatory disorders.Cell Research(from reference)Cell lines：bone marrow-derived dendritic cells (BMDCs) Concentrations：1 μM Incubation Time：24 hr |
| 体内研究： |
YKL-05-099 在浓度低于 10 μM 时无毒，并且在小鼠肝微粒体中稳定超过 2 小时。YKL-05-099 高度可溶 (PBS 溶解度=428 μM)，并以未结合状态存在于小鼠血浆中，浓度可观。YKL-05-099 剂量依赖性地降低 SIK 调节位点 Ser259 处 HDAC5 的磷酸化；在最低剂量 (5 mg/Kg) 时观察到磷酸化减少，并且在 20 mg/Kg 剂量开始时低于免疫印迹检测的限度。YKL-05-099 从 5 mg/Kg 开始剂量依赖性地降低血清中 TNFα 的丰度，并在 20 mg/Kg 剂量下将 IL-10 水平增加超过 2 倍。 |
| 参考文献： |
1. Sundberg TB, et al. Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo. ACS Chem Biol. 2016 Aug 19;11(8):2105-11. |
| 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 |
1.666 ml |
8.332 ml |
16.664 ml |
| 5 mM |
0.333 ml |
1.666 ml |
3.333 ml |
| 10 mM |
0.167 ml |
0.833 ml |
1.666 ml |
| 50 mM |
0.033 ml |
0.167 ml |
0.333 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