|3-(2-氯-6-甲基苯基)-7-((2-甲氧基-4-(1-甲基哌啶-4-基)苯基)氨基)-1-(5-甲氧基吡啶-2-基)-3,4-二氢嘧啶并[4,5-d]嘧啶-2(1H)-酮|CsnPharm

CAS No.: 1936529-65-5

YKL-05-099 Catalog No. CSN28431

Synonyms: Ykl-05-099

YKL-05-099 is a selective SIK inhibitor with IC50 values of 10 nM, 40 nM and 30 nM for SIK1, SIK2 and SIK3, respectively.

规格	价格	促销价格	库存	数量

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

加入购物车大规格询价

加入收藏

产品咨询

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

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].
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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.6664 mL
- 8.3318 mL
- 16.6636 mL
- 5 mM
- 0.3333 mL
- 1.6664 mL
- 3.3327 mL
- 10 mM
- 0.1666 mL
- 0.8332 mL
- 1.6664 mL

技术信息

CAS号	1936529-65-5	储存条件	粉末 Keep in dark place,Sealed in dry,2-8°C 液体 -20°C:3-6 月 -80°C:12月
分子式	C32H34ClN7O3	运输	蓝冰
分子量	600.11	别名	Ykl-05-099

大规格询价

号为必填项

姓名: 邮箱: 手机号:

留言:

提交

YKL-05-099 Catalog No. CSN28431

靶点选择性

请登录您的专属账户

确认信息