HG-9-91-01
(Synonyms: N-(2,4-二甲氧基苯基)-N'-(2,6-二甲基苯基)-N-[6-[[4-(4-甲基-1-哌嗪基)苯基]氨基]-4-嘧啶基]脲,SIK inhibitor 1) 目录号 : GC11719
An inhibitor of salt-inducible kinases
Cas No.:1456858-58-4
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
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Cell lines |
Bone marrow-derived macrophages |
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Preparation Method |
Powder was dissolved in DMSO as 10 mM stock solutions and stored at -20℃ until use. BMM cells were plated at concentration of 160 x 103 cells/well in 24 wells osteo assay plates coated with bone biomimetic synthetic surface and cultured with rmM-CSF (30ng/ml) and rmRANKL (50ng/ml) for 3 days in absence or presence of different concentrations of HG-9-91-01. |
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Reaction Conditions |
0, 0.1, 0.3, 0.5µM for 72 days |
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Applications |
No significant toxicity was observed at the concentrations tested. Pre-treatment with 0.5 µM HG-9-91-01 significantly reduced the formation of resorption lacunae compared to RANKL alone. |
| Animal experiment [2]: | |
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Animal models |
TNBS-induced colitis in female BALB/c mice, C57BL/6J mice |
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Preparation Method |
The TNBS-challenged mice were treated with different doses of HG-9-91-01 (3, 10, 30 mg/kg/day intraperitoneally (i.p.), dissolved in 100 µL olive oil). |
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Dosage form |
Intraperitoneal injection, 3, 10, 30 mg/kg/day for 8 days. |
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Applications |
TNBS-treated mice given HG-9-91-01 at 3, 10, or 30 mg/kg rapidly recovered their lost body weight. The macroscopic inflammatory signs (gross bleeding, ulceration) and the shortening of colon length typically caused by TNBS were also improved by treatment with 3, 10, or 30 mg/kg HG-9-91-01 |
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References: [1]: 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. |
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| Cas No. | 1456858-58-4 | SDF | |
| 别名 | N-(2,4-二甲氧基苯基)-N'-(2,6-二甲基苯基)-N-[6-[[4-(4-甲基-1-哌嗪基)苯基]氨基]-4-嘧啶基]脲,SIK inhibitor 1 | ||
| 化学名 | (Z)-N-(2,4-dimethoxyphenyl)-N'-(2,6-dimethylphenyl)-N-(6-((4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)carbamimidic acid | ||
| Canonical SMILES | CC1=C(/N=C(O)/N(C2=NC=NC(NC3=CC=C(N4CCN(CC4)C)C=C3)=C2)C5=C(OC)C=C(OC)C=C5)C(C)=CC=C1 | ||
| 分子式 | C32H37N7O3 | 分子量 | 567.68 |
| 溶解度 | ≥ 56.8mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7616 mL | 8.8078 mL | 17.6156 mL |
| 5 mM | 0.3523 mL | 1.7616 mL | 3.5231 mL |
| 10 mM | 0.1762 mL | 0.8808 mL | 1.7616 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet