HG-9-91-01 is effective against a range of protein tyrosine kinases featuring a threonine residue at the gatekeeper position, including Src family kinases (Src, Lck, Yes), BTK, and receptors for FGF and Ephrin[1]. HG-9-91-01 can potentiate IL-10 production in bone marrow-derived dendritic cells (BMDCs) when pre-treated with zymosan, showing an EC50 of ~200 nM, an effect comparable to that induced by PGE2, suggesting a strong link between SIK2 inhibition and enhanced IL-10 production[2]. HG-9-91-01 exhibits significant selectivity for SIKs over AMPK in cell-free assays, with an over 100-fold higher potency against SIKs (IC50 against AMPK = 4.5 μM). Treatment with HG-9-91-01 dose-dependently increases mRNA expression of Pck1 and G6pc and glucose production[3].
体外研究
HG-9-91-01 is effective against a range of protein tyrosine kinases featuring a threonine residue at the gatekeeper position, including Src family kinases (Src, Lck, Yes), BTK, and receptors for FGF and Ephrin[1].
HG-9-91-01 can potentiate IL-10 production in bone marrow-derived dendritic cells (BMDCs) when pre-treated with zymosan, showing an EC50 of ~200 nM, an effect comparable to that induced by PGE2, suggesting a strong link between SIK2 inhibition and enhanced IL-10 production[2].
HG-9-91-01 exhibits significant selectivity for SIKs over AMPK in cell-free assays, with an over 100-fold higher potency against SIKs (IC50 against AMPK = 4.5 μM). Treatment with HG-9-91-01 dose-dependently increases mRNA expression of Pck1 and G6pc and glucose production[3].
HG-9-91-01 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Peritoneal macrophages
1 µM
12 hours
HG-9-91-01 blocked TLR4-induced necroptosis
Cell Death Dis. 2022 Feb 25;13(2):188.
HT-29 cells
5 µM
HG-9-91-01 blocked TNF-induced necroptosis
Cell Death Dis. 2022 Feb 25;13(2):188.
Bone marrow-derived macrophages (BMDMs)
500 nM
1 hour
Increased IL-10 production and suppressed proinflammatory cytokine secretion
Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16986-91.
RAW264.7 macrophages
500 nM
1 hour
Increased IL-10 production via a CRTC3-dependent mechanism
Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):16986-91.
Mouse islet cells
1 µM
48 or 96 hours
To assess the effect of HG-9-91-01 on the proliferation of mouse islet cells, results showed that HG-9-91-01 significantly increased the percentages of both Ki67+ and EdU+ β cells at 96 h.
Nat Metab. 2021 May;3(5):682-700.
Human islet cells
1 µM
96 hours
To assess the effect of HG-9-91-01 on the proliferation of human islet cells, results showed that HG-9-91-01 significantly increased the percentage of Ki67+ β cells.
Nat Metab. 2021 May;3(5):682-700.
HG-9-91-01 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Wild-type C57BL/6J mice
Subcutaneous
10 mg/kg/day
Continuous for 7 days
To assess the effect of HG-9-91-01 on β cell proliferation in mice, results showed that HG-9-91-01 significantly increased the percentage of BrdU+ β cells.
Nat Metab. 2021 May;3(5):682-700.
Mice
TNF-induced systemic inflammatory response syndrome (SIRS) model
Intraperitoneal injection
5 mg/kg
Single injection, continuous observation
Mice pretreated with HG-9-91-01 showed resistance to TNF-induced systemic inflammatory response syndrome
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