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].
YKL-06-061 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse melanoma B16F0 cells
3 µM ARN 3236 or 1 µM YKL 06-061
72 hours
To investigate the inhibitory effect of Yakuchinone A on SIK inhibitor-induced melanogenesis. Results showed that Yakuchinone A inhibited melanin production in SIK inhibitor-activated B16F0 cells.
Int J Biol Sci. 2024 Jan 1;20(1):312-330
YKL-06-061 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
PTZ-induced epilepsy model
Intraperitoneal injection
10, 20, or 40 mg/kg
7 days
YKL-06-061 decreased seizure activity and prevented neuronal overactivity
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