YKL-05-099 - Salt-inducible Kinase (SIK) 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEYKL-05-099Cat. No.: HY-101147CAS No.: 1936529-65-5分式: CHClNO分量: 600.11作靶点: Salt-inducible Kinase (SIK)作通路: Immunology/Inflammation储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 75 mg/mL (1

2、24.98 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.17 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.17 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolu

3、bility: 2.5 mg/mL (4.17 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 YKL-05-099种盐诱导型激酶 (SIK) 探针。YKL-05-099 作于SIK1 和 SIK3，IC50 分别约为 10 和 30 nM。YKL-05-099 抑制 SIK2 的活性稍低，IC50 值为 40 nM 1。IC50 & Target IC50: 10 nM (SIK1), 30 nM (SIK3), 40 nM (SIK2) 1体外研究 YKL-05-099 has slightly less potent SIK2-inhibitory (

4、IC50=40 nM) and IL-10-enhancing activities (EC50=460nM). YKL-05-099 binds to SIK1 and SIK3 with IC50s of 10 and 30 nM, respectively, in a competitive bindingassay. Preincubating bone marrow-derived macrophages with YKL-05-099 reduces LPS stimulatedphosphorylation of HDAC5 at the SIK-specific phospho

5、rylation site Ser259. YKL-05-099 suppressesproduction of the inflammatory cytokines TNF, IL-6 and IL-12p40, and only modestly enhances IL-1release in BMDCs stimulated with the yeast cell wall extract Zymosan A 1.体内研究 YKL-05-099 is non-toxic at concentrations less than 10 M and stable in mouse liver

6、microsomes for morethan 2 hours. YKL-05-099 is highly soluble (PBS solubility=428 M) and present in an unbound state atappreciable levels in mouse plasma. YKL-05-099 dose dependently decreases phosphorylation of HDAC5 atthe SIK-regulated site Ser259; reduced phosphorylation is observed at the lowest

7、 dose (5 mg/Kg) and isbelow the limit of detection by immunoblotting beginning at the 20 mg/Kg dose. YKL-05-099 dose-dependently reduces abundance of TNF in serum beginning at 5 mg/Kg, and increases IL-10 levels at the20 mg/Kg dose by more than 2-fold 1.PROTOCOLAnimal Mice: YKL-05-099 is diluted in

8、5% N-methyl-2-pyrrolidinone, 5% Solutol HS15 and 90% normal saline andAdministration 1 administered IP to male 810 week-old C57BL/6 mice. Serum and tissue samples are collected aftereuthanizing mice by CO2 inhalation overdose followed by cervical dislocation 1.MCE has not independently confirmed the

9、 accuracy of these methods. They are for reference only.户使本产品发表的科研献 Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Sundberg TB, et al. Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo. ACS Chem Biol. 2016Aug 19;11(8):2105-11.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMcePdfHeightCaution: Product has not been fully validated for m