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Synonyms | SIK inhibitor 1 | Storage (From the date of receipt) |
3 years -20°C powder | ||||||||
化学式 | C32H37N7O3 |
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分子量 | 567.68 | CAS No. | 1456858-58-4 | ||||||||
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (176.15 mM) | ||||||||
Water | Insoluble | ||||||||||
Ethanol | Insoluble | ||||||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | HG-9-91-01 (SIK inhibitor 1) is a potent and highly selective inhibitor of salt-inducible kinase (SIK) with IC50 of 0.92 nM, 6.6 nM and 9.6 nM for SIK1, SIK2 and SIK3, respectively. |
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in vitro | HG-9-91-01 is a potent and selective inhibitor of SIK. HG-9-91-01 not only targets the ATP-binding site, but also a small hydrophobic pocket adjacent to this site that is created by the presence of a small amino acid residue at this gatekeeper site. HG-9-91-01 inhibits a number of protein tyrosine kinases that possess a threonine residue at the gatekeeper site, such as Src family members (Src, Lck, and Yes), BTK, and the FGF and Ephrin receptors. HG-9-91-01 potently inhibits the SIKs and, crucially, does not inhibit any other member of the AMPK-related kinase subfamily, which all possess a large hydrophobic residue (Met or Leu) at the gatekeeper site. HG-9-91-01 increases LPS-stimulated IL-10 production and greatly suppressed proinflammatory cytokine secretion, even when cells are costimulated with IFNγ to generate fully polarized classically activated (M1) macrophages.[1] |
in vivo | HG-9-91-01 is > 99% serum bound and rapidly degraded by mouse liver microsomes (t1/2 = 11 min) making this compound unsuitable for direct injection into animals.[2] |
細胞アッセイ | 細胞株 | Macrophages |
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濃度 | 500 nM | |
反応時間 | 1 h | |
実験の流れ | Macrophages are treated for 1 h with 500 nM HG-9-91-01 or an equivalent volume of DMSO for control incubations then stimulated for up to 24 h with 1 μg/mL Pam3CSK4, 2 μg/mL lipoteichoic acid (LTA), 100 ng/mL LPS, 1 μg/mL R837, or 2 μM CpG. Proteins are extracted and immunoblotted by using the indicated antibodies. RNA is extracted by using the RNeasy Micro Kit. cDNA is generated by using the iScript cDNA synthesis kit and quantified by qPCR using the SsoFast EvaGreen Supermix. The relative expression of each gene is calculated from Ct values by using the Pfaffl method and is normalized against the mRNA levels of 18S or GAPDH RNA. Fold induction for each gene is reported relative to untreated control cells, which is set to 1. The concentrations of TNFα, IL-6, IL-10, IL-12p40, and RANTES in culture supernatants were measured by using the Bio-Plex Pro Assay system from Bio-Rad. |
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動物実験 | 動物モデル | male 8-10 week-old C57BL/6 mice |
投薬量 | -- | |
投与方法 | IP |
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Dynamic chromatin architecture identifies new autoimmune-associated enhancers for IL2 and novel genes regulating CD4+ T cell activation [ bioRxiv, 2023, 10.1101/2023.04.05.535731] | PubMed: none |
Salt-inducible kinase inhibition sensitizes human acute myeloid leukemia cells to all-trans retinoic acid-induced differentiation [ Int J Hematol, 2020, 10.1007/s12185-020-03026-1] | PubMed: 33074481 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。