YKL-05-099 是盐诱导型激酶 (SIK) 抑制剂。能够抑制SIK1(IC50:10 nM)、SIK3(IC50:30 nM)的活性，对SIK2(IC50:40 nM) 的活性抑制作用稍弱。

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 (IC50:40 nM).

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 [1].

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 [1].

1936529-65-5

C32H34ClN7O3

600.11

DMSO:75 mg/mL (124.98 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years