| 产品描述： | HG-9-91-01 (SIK inhibitor 1) 是一种有效且高度选择性的 salt-inducible kinase (SIK) 的抑制剂，对SIK1、SIK2和SIK3的IC50值分别为0.92 nM、6.6 nM和9.6 nM |
| 靶点： |
SIK1(Cell-free assay):0.92 nM; SIK2 (Cell-free assay):6.6 nM; SIK3(Cell-free assay):9.6 nM;SIK |
| 体外研究： |
HG-9-91-01 is a potent and selective inhibitor of SIK. HG-9-91-01 not only targets the ATP-binding site, but also a small hydrophobic pocket adjacent to this site that is created by the presence of a small amino acid residue at this gatekeeper site. HG-9-91-01 inhibits a number of protein tyrosine kinases that possess a threonine residue at the gatekeeper site, such as Src family members (Src, Lck, and Yes), BTK, and the FGF and Ephrin receptors. HG-9-91-01 potently inhibits the SIKs and, crucially, does not inhibit any other member of the AMPK-related kinase subfamily, which all possess a large hydrophobic residue (Met or Leu) at the gatekeeper site. HG-9-91-01 increases LPS-stimulated IL-10 production and greatly suppressed proinflammatory cytokine secretion, even when cells are costimulated with IFNγ to generate fully polarized classically activated (M1) macrophages |
| 体内研究： |
HG-9-91-01 is > 99% serum bound and rapidly degraded by mouse liver microsomes (t1/2 = 11 min) making this compound unsuitable for direct injection into animals |
| 细胞实验： |
Cell lines: Macrophages Concentrations: 500 nM Incubation Time: 1 h Method: Macrophages are treated for 1 h with 500 nM HG-9-91-01 or an equivalent volume of DMSO for control incubations then stimulated for up to 24 h with 1 μg/mL Pam3CSK4, 2 μg/mL lipoteichoic acid (LTA), 100 ng/mL LPS, 1 μg/mL R837, or 2 μM CpG. Proteins are extracted and immunoblotted by using the indicated antibodies. RNA is extracted by using the RNeasy Micro Kit. cDNA is generated by using the iScript cDNA synthesis kit and quantified by qPCR using the SsoFast EvaGreen Supermix. The relative expression of each gene is calculated from Ct values by using the Pfaffl method and is normalized against the mRNA levels of 18S or GAPDH RNA. Fold induction for each gene is reported relative to untreated control cells, which is set to 1. The concentrations of TNFα, IL-6, IL-10, IL-12p40, and RANTES in culture supernatants were measured by using the Bio-Plex Pro Assay system from Bio-Rad. |
| 动物实验： |
Animal Models: male 8-10 week-old C57BL/6 mice Dosages: -- Administration: IP |
| 参考文献： |
1. Kristopher Clark, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16986-91. 2. Thomas B Sundberg, 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. |
| 溶解性： |
Soluble in DMSO |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.762 ml |
8.808 ml |
17.616 ml |
| 5 mM |
0.352 ml |
1.762 ml |
3.523 ml |
| 10 mM |
0.176 ml |
0.881 ml |
1.762 ml |
| 50 mM |
0.035 ml |
0.176 ml |
0.352 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