| CAS NO: | 1936529-65-5 |
| 规格: | ≥98% |
| Name: YKL-05-099 CAS#: 1936529-65-5 Chemical Formula: C32H34ClN7O3 Exact Mass: 599.2412 Molecular Weight: 600.12 | |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Technical Information | Synonym: YKL05099;YKL-05-099; YKL 05 099; Chemical Name: 3-(2-Chloro-6-methylphenyl)-7-((2-methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-1-(5-methoxypyridin-2-yl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one InChi Key: VQINULODWGEVBB-UHFFFAOYSA-N InChi Code: InChI=1S/C32H34ClN7O3/c1-20-6-5-7-25(33)29(20)39-19-23-17-35-31(37-30(23)40(32(39)41)28-11-9-24(42-3)18-34-28)36-26-10-8-22(16-27(26)43-4)21-12-14-38(2)15-13-21/h5-11,16-18,21H,12-15,19H2,1-4H3,(H,35,36,37) SMILES Code: O=C1N(C2=NC=C(OC)C=C2)C3=NC(NC4=CC=C(C5CCN(C)CC5)C=C4OC)=NC=C3CN1C6=C(C)C=CC=C6Cl |
| Target | IC50: 40 nM (SIK2)[1] |
|---|---|
| In Vitro | YKL-05099 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 with IC50s of 10 and 30 nM, respectively, in a competitive binding assay. Preincubating bone marrow-derived macrophages with YKL-05-099 reduces LPS stimulated phosphorylation of HDAC5 at the SIK-specific phosphorylation site Ser259. YKL-05-099 suppresses 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[1]. |
| In Vivo | YKL-05-099 is non-toxic at concentrations less than 10 μM and stable in mouse liver microsomes for more than 2 hours. 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 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. YKL-05-099 dose-dependently reduces 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[1]. |
| Animal Protocol | Mice: YKL-05-099 is diluted in 5% N-methyl-2-pyrrolidinone, 5% Solutol HS15 and 90% normal saline and administered IP to male 8–10 week-old C57BL/6 mice. Serum and tissue samples are collected after euthanizing mice by CO2 inhalation overdose followed by cervical dislocation[1]. |
| References | [1]. Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo. ACS Chem Biol. 2016 Aug 19;11(8):2105-11 |
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