HG-9-91-01
HG-9-91-01 is a pan-SIK (salt-inducible kinases) inhibitor with IC50 values of 0.92nM, 6.6nM and 9.6nM for SIK1, SIK2, SIK3, respectively [1].
SIKs restrict the formation of regulatory macrophages. The inhibition of these enzymes is thought to have potential for treating inflammatory and autoimmune diseases. HG-9-91-01 potently inhibits SIKs through targeting both the ATP-binding site and the small hydrophobic pocket. It is reported that, besides SIKs, HG-9-91-01 also inhibits various protein tyrosine kinases such as Src, BTK, FGF and Ephrin receptors. But other AMPK-related kinase subfamily members are not sensitive to HG-9-91-01. HG-9-91-01 can promote LPS-stimulated IL-10 production, CREB-dependent gene transcription, inhibit proinflammatory cytokine secretion and induce the expression of regulatory macrophage markers [1].
References:
[1] 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. Proceedings of the National Academy of Sciences, 2012, 109(42): 16986-16991.
- 1. Xing Tu, Zixing Zou, et al. "Artificial intelligence-enabled discovery of a RIPK3 inhibitor with neuroprotective effects in an acute glaucoma mouse model." Chin Med J (Engl). 2025 Jan 20;138(2):172-184. PMID: 39719694
- 2. Caterina Iorio, Jillian L. Rourke, Met al. "Silencing the G-protein coupled receptor 3-salt inducible kinase 2 pathway promotes human β cell proliferation." Commun Biol. 2021 Jul 23;4(1):907. PMID:34302056
- 3. Wang Z, Ma J, Met al. "Quantitative phosphoproteomic analysis of the molecular substrates of sleep need." Nature. 2018 Jun;558(7710):435-439. PMID:29899451
- 4. Abend A, Shkedi O, et al. "Salt-inducible kinase induces cytoplasmic histone deacetylase 4 to promote vascular calcification." EMBO Rep.2017 Jul;18(7):1166-1185. PMID:28588072
| Storage | Store at -20°C |
| M.Wt | 567.68 |
| Cas No. | 1456858-58-4 |
| Formula | C32H37N7O3 |
| Solubility | ≥56.8 mg/mL in DMSO; ≥27.3 mg/mL in EtOH; ≥6.35 mg/mL in H2O with ultrasonic |
| 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 |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Macrophages |
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Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
1 h |
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Applications |
HG-9-91-01increases LPS-stimulated IL-10 production and markedly inhibits proinflammatory cytokine secretion even when WT SIK2 is expressed to the same level. In addition, CRTC3 is required for HG-9-91-01 to enhance IL-10 production in LPS-stimulated primary mouse macrophages. |
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References: 1. Clark K, MacKenzie KF, Petkevicius K et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16986-91. |
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