GSK583

製品コードS8261 バッチS826101

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₀H₁₉FN₄O₂S

分子量

398.45

CAS No.

1346547-00-9

Solubility (25°C)*

体外

DMSO

79 mg/mL (198.26 mM)

Ethanol

28 mg/mL (70.27 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	GSK583は、IC50が5 nMである、RIP2キナーゼの非常に強力で選択的な阻害剤です。GSK583はまた、摘出培養物において、TNF-αとIL-6の両方の産生をIC50約200 nMで阻害します。
in vitro	GSK583 possesses comparable binding affinity for RIP3 kinase as demonstrated by an in-house FP binding assay configured similarly to the RIP2 FP assay (RIP2 FP IC50 = 5 nM; RIP3 FP IC50 = 16 nM). Despite this potent biochemical activity against RIP3 kinase, this compound shows little or no inhibition of RIP3-dependent necroptotic cell death in a cellular assay up to 10 μM concentration. It potently and dose dependently inhibits MDP-stimulated tumor necrosis factor-alpha (TNFα) production with an IC50 = 8 nM in primary human monocytes. Following treatment with this chemical at 1 μM, little inhibition of pro-inflammatory signaling is observed upon activation of Toll-like receptors (TLR2, TLR4, TLR7) or cytokine receptors (IL-1R, TNFR) but complete inhibition is observed upon activation of both NOD1 and NOD2 receptors, which signal in a RIP2-dependent manner. Although it has excellent kinase selectivity, this compound does inhibit both the hERG channel and Cyp3A4, which precludes it from further progression as a drug candidate.
in vivo	GSK583 has low clearance, moderate volumes of distribution, and moderate oral bioavailability in both rat and mouse. Eventhough this compound would not produce a human phamacodynamic response within an acceptable dose range which precludes this molecule from further development as a drug candidate, the oral PK in rat and mouse provides sufficient systemic exposure for use as a preclinical in vivo tool molecule in an acute inflammation challenge model.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	primary human monocytes
	濃度	1 μM
	反応時間	30 min
	実験の流れ	To assess cellular selectivity, monocytes are pretreated with this compound for 30 min, then stimulated for 6 h with ligands which selectively agonize NLRs NOD1, NOD2; Toll-like receptors TLR, TLR4, TLR7, or cytokine receptors IL-1R, TNFR. Release of pro-inflammatory cytokines, either TNFα (NOD2, TLR2, TLR4, IL1R) or IL-8 (NOD1, TLR7, TNFR), is measured by immunoassay. Percent inhibition and/or IC50 values are calculated.
動物実験	動物モデル	C57BL/6 mice
	投薬量	0.1, 1, 10 and 100 mg/kg
	投与方法	oral administration

参考

https://pubmed.ncbi.nlm.nih.gov/27109867/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

NOD2-induced IκBζ mediates a protective host response against epicutaneous Staphylococcus aureus infection [ J Invest Dermatol, 2025, S0022-202X(25)00494-4]	PubMed: 40412468
Deletion of Glutathione S-Transferase Omega 1 Activates Type I Interferon Genes and Downregulates Tissue Factor [ Cancer Res, 2020, canres.530.2020]	PubMed: 32571799
NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice [ J Neuroinflammation, 2020, 17(1):364]	PubMed: 33261639

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。