Accueil>>Signaling Pathways>> Immunology/Inflammation>> SIKs>>HG-9-91-01

HG-9-91-01

Catalog No.GC11719

HG-9-91-01 est un inhibiteur puissant et hautement sélectif de la kinase inductible par le sel (SIK) avec des IC50 de 0,92 nM, 6,6 nM et 9,6 nM pour SIK1, SIK2 et SIK3 respectivement.

Products are for research use only. Not for human use. We do not sell to patients.

HG-9-91-01 Chemical Structure

Cas No.: 1456858-58-4

Taille Prix Stock Qté
10mM(in 1mL DMSO)
171,00 $US
En stock
1mg
53,00 $US
En stock
2mg
103,00 $US
En stock
5mg
137,00 $US
En stock
10mg
221,00 $US
En stock
50mg
557,00 $US
En stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

Bone marrow-derived macrophages

Preparation Method

Powder was dissolved in DMSO as 10 mM stock solutions and stored at -20¡栵ntil 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.

Reaction Conditions

0, 0.1, 0.3, 0.5µM for 72 days

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]:

Animal models

TNBS-induced colitis in female BALB/c mice, C57BL/6J mice

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).

Dosage form

Intraperitoneal injection, 3, 10, 30 mg/kg/day for 8 days.

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

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.
[2]: 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.

Background

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.

Chemical Properties

Cas No. 1456858-58-4 SDF
Chemical Name (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
Formula C32H37N7O3 M.Wt 567.68
Solubility ≥ 56.8mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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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
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Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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