HG-9-91-01 is a salt-inducible kinases (SIK) inhibitor, inhibited SIK1, SIK2, SIK3 with IC50 values of 0.92nM, 6.5nM and 19.4nM, respectively [1].
HG-9-91-01 potently inhibited the SIKs and did not inhibit any other member of the AMPK-related kinase subfamily. HG-9-91-01 increased LPS-stimulated IL-10 production and suppressed proinflammatory cytokine secretion [2]. 0.5 µM HG-9-91-01 pretreated RAW264.7 for 30 min before RANKL stimulation resulted in reduction of multinucleated cell formation and of TRAP staining, and significantly reduced the mRNA of osteoclast differentiation markers in a concentration dependent manner. Pre-treatment with 0.5 µM HG-9-91-01 significantly reduced the formation of resorption lacunae compared to RANKL alone [3].
HG-9-91-01 (3, 10, or 30 mg/kg) enhanced the expression of IL-10 whereas downregulated the levels of IL-12 and TNF-α in the colon tissue of the TNBS mice [4].
References:
[1]. Sundberg T B, Choi H G, Song J H, et al. Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells[J]. Proceedings of the National Academy of Sciences, 2014, 111(34): 12468-12473.
[2]. Clark K, MacKenzie K F, Petkevicius K, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages[J]. Proceedings of the National Academy of Sciences, 2012, 109(42): 16986-16991.
[3]. Lombardi M S, GilliÉron C, Berkelaar M, et al. Salt-inducible kinases (SIK) inhibition reduces RANKL-induced osteoclastogenesis[J]. PloS one, 2017, 12(10): e0185426.
[4]. Fu Y, Ma G, Zhang Y, et al. HG-9-91-01 Attenuates murine experimental colitis by promoting interleukin-10 production in colonic macrophages through the SIK/CRTC3 pathway[J]. Inflammatory Bowel Diseases, 2021, 27(11): 1821-1831.
HG-9-91-01 是一种盐诱导激酶 (SIK) 抑制剂，可抑制 SIK1、SIK2、SIK3，IC50 值分别为 0.92nM、6.5nM 和 19.4nM[1].
HG-9-91-01 有效抑制 SIK，但不抑制 AMPK 相关激酶亚家族的任何其他成员。 HG-9-91-01 增加 LPS 刺激的 IL-10 产生并抑制促炎细胞因子分泌[2]。 0.5 µM HG-9-91-01 在 RANKL 刺激之前将 RAW264.7 预处理 30 分钟导致多核细胞形成和 TRAP 染色减少，并以浓度依赖性方式显着减少破骨细胞分化标志物的 mRNA。与单独使用 RANKL 相比，使用 0.5 µM HG-9-91-01 进行预处理可显着减少吸收陷窝的形成[3]。
HG-9-91- 01（3、10 或 30 mg/kg）增强 IL-10 的表达，同时下调 IL-12 和 TNF-α 的水平；在TNBS小鼠结肠组织中[4]。