YKL-05-099

YKL-05-099 is an inhibitor of salt-inducible kinase 2 (SIK2; IC₅₀ = 0.04 ?M for the human enzyme).¹ It is selective for SIK2 over a panel of 141 kinases at 1 ?M but also inhibits 14 other kinases, including SIK3, Ephrin receptors, and Src. YKL-05-099 increases IL-10 production in zymosan A-induced isolated mouse bone marrow-derived dendritic cells (BMDCs; EC₅₀ = 0.46 ?M), as well as decreases TNF-α, IL-6, and IL-12p40 levels and increases IL-1β levels in LPS-stimulated BMDCs when used at a concentration of 1 ?M. It inhibits the proliferation of MOLM-13 leukemia cells (IC₅₀ = 0.24 ?M).² In vivo, YKL-05-099 (10 ?mol/kg) increases the bone formation rate and number of femoral osteoblasts and decreases the number of femoral osteoclasts in mice.³

1.Sundberg, T.B., Liang, Y., Wu, H., et al.Development of chemical probes for investigation of salt-inducible kinase function in vivoACS Chem. Biol.11(8)2105-2111(2016) 2.Tarumoto, Y., Lin, S., Wang, J., et al.Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivoBlood135(1)56-70(2020) 3.Wein, M.N., Liang, Y., Goransson, O., et al.SIKs control osteocyte responses to parathyroid hormoneNat. Commun.713176(2016)