| Identification | Back Directory | [Name]
YKL-05-099 | [CAS]
1936529-65-5 | [Synonyms]
YKL-05-099
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
Pyrimido[4,5-d]pyrimidin-2(1H)-one, 3-(2-chloro-6-methylphenyl)-3,4-dihydro-7-[[2-methoxy-4-(1-methyl-4-piperidinyl)phenyl]amino]-1-(5-methoxy-2-pyridinyl)- | [Molecular Formula]
C32H34ClN7O3 | [MOL File]
1936529-65-5.mol | [Molecular Weight]
600.11 |
| Chemical Properties | Back Directory | [Boiling point ]
761.0±70.0 °C(Predicted) | [density ]
1.311±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO:103.33(Max Conc. mg/mL);172.18(Max Conc. mM) | [form ]
A solid | [pka]
8.63±0.20(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
YKL-05-099 is a salt-inducible kinase (SIK) inhibitor. YKL-05-099 binds to SIK1 and SIK3 with IC50s of ~10 and ~30 nM, respectively. YKL-05-099 has slightly less potent SIK2-inhibitory (IC50=40 nM)[1]. | [Biological Activity]
Potent and selective salt-inducible kinases (SIK1SIK2SIK3) inhibitor in vitro and in vivo.
YKL-05-099 is a potent and selective salt-inducible kinases inhibitor (SIK1/2/3 IC50 = 10/40/30 nM) with superior pharmacokinetic properties than HG-9-91-01. YKL-05-099 pre-treatment of murine BDMCs up-regulates Zymosan A-stimulated IL-10 (EC50 = 460 nM with 24h )while suppresses inflammatory cytokines production (TNFαIL-6 and IL-12p40). LikewiseYKL-05-099 intraperitoneal administration in mice (20 mg/kg i.p.) 15 min prior to LPS (0.5 mg/kg i.p.) enhances serum IL-10while reduces HDAC5 pSer259 levels in total splenic leukocytes and serum TNFα level in vivo. | [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]. | [IC 50]
SIK1; SIK3 | [storage]
Store at -20°C | [References]
[1] 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. DOI:10.1021/acschembio.6b00217 |
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| Company Name: |
ChemCell Biomedicine Co.,Ltd.
|
| Tel: |
020-13556033878 2965585218 13556033878 |
| Website: |
www.chemicalbook.com/ShowSupplierProductsList15061/0_EN.htm |
| Company Name: |
Twochem Co.Ltd.
|
| Tel: |
021-58111628 15800915896 |
| Website: |
cn.twochem.com |
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