Salt-inducible kinases (SIK) constitute a subfamily of kinases comprising three members (SIK1, -2, and -3). Inhibition of SIK kinase activity induces an anti-inflammatory phenotype in macrophages[1]. SIK has also been demonstrated to regulate MITF (microphthalmia-associated transcription factor), the master regulator of pigment gene expression, through its effects on CRTC (cAMP-regulated transcriptional co-activators) and CREB (cAMP-responsive element-binding protein) activity[2]. YKL-06-061 is a potent, selective, second-generation SIK inhibitor with IC50 values of 6.56 nM/1.77 nM/20.5 nM for SIK1/2/3, respectively[2]. Both in UACC62 human melanoma cells and UACC257 human melanoma cells, YKL 06-061 yields a dose-dependent increase in MITF mRNA expression after continuous 3 hours exposure to drug concentrations of 0-4 μM and 0-16 μM, respectively[2].
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