PF-3644022

製品コードS8224 バッチS822401

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₂₁H₁₈N₄OS
	分子量	374.46	CAS No.	1276121-88-0
Solubility (25°C)*	体外	DMSO	75 mg/mL (200.28 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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	PF-3644022 is a potent freely reversible ATP-competitive inhibitor of MAPKAPK2 (MK2) with an Ki of 3 nM. PF-3644022 also potently inhibits TNFα production with an IC50 of 160 nM.
in vitro	PF-3644022 is a potent freely reversible ATP-competitive compound that inhibits Mitogen-activated protein kinase-activated protein kinase 2(MK2) activity with good selectivity when profiled against 200 human kinases. In the human U937 monocytic cell line or peripheral blood mononuclear cells, PF-3644022 potently inhibits TNFα production with similar activity. PF-3644022 blocks TNFα and IL-6 production in LPS-stimulated human whole blood.<sup><a class="sref" href="#s_ref">[1]</a></sup>
in vivo	PF-3644022 displays good pharmacokinetic parameters in rats and is orally efficacious in both the rat acute LPS-induced TNFα model and the chronic streptococcal cell wall-induced arthritis model,with ED50 values of 6.9 and 20 mg/kg, respectively.<sup><a class="sref" href="#s_ref">[1]</a></sup>

プロトコル(参考用のみ)

キナーゼアッセイ	In Vitro Kinase Assays and Inhibition Kinetics.
キナーゼアッセイ	The kinase activity of MK2 is assayed by using fluorescently labeled heat shock protein 27 (HSP27) peptide and a Caliper LabChip 3000. Phosphorylated peptide is separated from substrate peptide electrophoretically and quantified. All kinase reactions are performed at room temperature in 20 mM HEPES, containing 10 mM MgCl2, 1 mM dithiothreitol, 0.01% bovine serum albumin, and 0.0005% Tween 20, pH 7.5. For endpoint experiments, reactions are terminated during the linear phase by the addition of 30 mM EDTA. The kinase selectivity experiments are performed with the MgATP concentration fixed at the Km(app) determined for each enzyme. The initial velocitie is determined in the presence and absence of PF-3644022 with ATP as the varied substrate while the HSP27 peptide concentration is held constant.
細胞アッセイ	細胞株	Human U937 monocytic cell line, hPBMCs
	濃度	0.1 nM-100μM
	反応時間	1 h
	実験の流れ	U937 cells and hPBMCs are pretreated with PF-3644022 at varying concentrations for 1 h before LPS stimulation at 100 ng/ml. TNFα levels in U937 cell are measured at 4 h after LPS stimulation by using an electrochemoluminescence MesoScale Discovery TNF kit. In hPBMCs, TNFα and IL-6, IL-8 are measured at 16 h after LPS stimulation by using a four-plex human cytokine MSD plate.
動物実験	動物モデル	LPS-induced acute endotoxemia inflammation model (adult male Lewis rats), chronic streptococcal cell wall-induced arthritis model (female Lewis rats)
	投薬量	1 mg/kg
	投与方法	Oral gavage

参考

[1] Robert J Mourey , et al. J Pharmacol Exp Ther . 2010 Jun;333(3):797-807.

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：

NLRP6 induces RIP1 kinase-dependent necroptosis via TAK1-mediated p38MAPK/MK2 phosphorylation in S. typhimurium infection [ iScience, 2024, 27(4):109339]	PubMed: 38500819

NLRP6 induces RIP1 kinase-dependent necroptosis via TAK1-mediated p38MAPK/MK2 phosphorylation in S. typhimurium infection [ iScience, 2024, 27(4):109339]

PubMed: 38500819

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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。

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