YKL-05-099
YKL-05-099 Basic information
- Product Name:
- YKL-05-099
- Synonyms:
-
- YKL-05-099
- 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)-
- 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
- YKL05099,YKL 05 099,inhibit,Salt-inducible Kinase (SIK),Inhibitor
- YKL-05-099, 10 mM in DMSO
- CAS:
- 1936529-65-5
- MF:
- C32H34ClN7O3
- MW:
- 600.11
- Mol File:
- 1936529-65-5.mol
YKL-05-099 Chemical Properties
- 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
YKL-05-099 Usage And Synthesis
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 (SIK1, SIK2, SIK3) 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 (TNFα, IL-6 and IL-12p40). Likewise, YKL-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-10, while 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
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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