YKL-05-099

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Chemical Structure| 1936529-65-5 同义名 : -
CAS号 : 1936529-65-5
货号 : A723778
分子式 : C32H34ClN7O3
纯度 : 98%
分子量 : 600.111
MDL号 : MFCD31382123
存储条件:

Pure form Keep in dark place,Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月

溶解度 :

DMSO: 80 mg/mL(133.31 mM),注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方:
生物活性
描述 Salt-inducible kinase (SIK), which belongs to the sucrose non-fermenting 1/AMP-activated protein kinase family, was first discovered in the adrenal cortex of a rat on a high-salt diet[2]. SIK1 has a role in the fine tuning of steroidogenic enzyme production during the initial phase of steroidogenesis. SIK2 is found in adipocytes and phosphorylates a specific serine residue in insulin receptor substrate-1[3]. YKL-05-099 is an inhibitor of the salt-inducible kinase(SIK1 and SIK3 ; IC50s: 10 and 30 nM, respectively). It has a slightly less potent SIK2-inhibitory (IC50:40nM). YKL-05-099 inhibits the production of the inflammatory cytokines TNFα, IL-6 and IL-12p40, and only modestly enhances IL-1β release in BMDCs stimulated with the yeast cell wall extract Zymosan A. YKL-05-099 has slightly less potent SIK2-inhibitory (IC50=40 nM) and IL-10-enhancing activities (EC50=460 nM). YKL-05-099 binds to SIK1 and SIK3 (IC50s: 10 and 30 nM, respectively, in a competitive binding assay). Preincubating bone marrow-derived macrophages with YKL-05-099 decreases LPS stimulated phosphorylation of HDAC5 at the SIK-specific phosphorylation site Ser259. YKL-05-099 is highly soluble (PBS solubility=428 μM) and present in an unbound state at appreciable levels in mouse plasma. YKL-05-099 is non-toxic at concentrations of less than 10 μM and stable in mouse liver microsomes for more than 2 hours. YKL-05-099 dose-dependently decreases the abundance of TNFα in serum beginning at 5 mg/Kg and increases IL-10 levels at the 20 mg/Kg dose by more than 2-fold. YKL-05-099 dose-dependently decreases phosphorylation of HDAC5 at the SIK-regulated site Ser259; reduced phosphorylation is observed at the lowest dose (5 mg/Kg) and is below the limit of detection by immunoblotting beginning at the 20 mg/Kg dose[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.67mL

0.33mL

0.17mL

8.33mL

1.67mL

0.83mL

16.66mL

3.33mL

1.67mL

参考文献

[1]Sundberg TB, Liang Y, Wu H, Choi HG, Kim ND, Sim T, Johannessen L, Petrone A, Khor B, Graham DB, Latorre IJ, Phillips AJ, Schreiber SL, Perez J, Shamji AF, Gray NS, Xavier RJ. Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo. ACS Chem Biol. 2016 Aug 19;11(8):2105-11. doi: 10.1021/acschembio.6b00217. Epub 2016 Jun 6. PMID: 27224444; PMCID: PMC4992440.

[2]Fangyu Chen,et al. Salt-Inducible Kinase 2: An Oncogenic Signal Transmitter and Potential Target for Cancer Therapy. Front Oncol. 2019 Jan 22;9:18.

[3]Mitsuhiro Okamoto,et al. Salt-inducible kinase in steroidogenesis and adipogenesis. Trends Endocrinol Metab.Jan-Feb 2004;15(1):21-6.

[4]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.