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.
