Decernotinib (VX-509)

製品コードS7541 バッチS754102

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	C₁₈H₁₉F₃N₆O
	分子量	392.38	CAS No.	944842-54-0
Solubility (25°C)*	体外	DMSO	78 mg/mL (198.78 mM)
		Ethanol	78 mg/mL warmed with 50ºC water bath (198.78 mM)
		Water	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	Decernotinib (VX-509) is a potent and selective JAK3 inhibitor with K_i of 2.5 nM, >4-fold selectivity over JAK1, JAK2, and TYK2, respectively. Phase 2/3.
in vitro	In HT-2 cells, Decernotinib inhibits IL-2–stimulated HT-2 STAT-5 phosphorylation, human T-cell blast proliferation, and CD40L/IL-4–induced B-cell proliferation. ^[1]
in vivo	In a rat model of collagen-induced arthritis, VX-509 (50 mg/kg, p.o.) results in dose-dependent reduction in ankle swelling and paw weight and improved paw histopathology scores. In a mouse model of oxazolone-induced delayed-type hypersensitivity, VX-509 (50 mg/kg, p.o.) significantly suppresses ear edema. ^[1] In a rat HvG model, VX-509 (50 mg/kg, p.o.) results in dose-dependent inhibition of popletial lymph node (PLN) hyperplasia. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase Activity Assays
キナーゼアッセイ	The effect of VX-509 on JAK3 activity is assessed by measuring the residual kinase activity of the recombinantly expressed JAK3 kinase domain using a radiometric assay. The final concentrations of the components in the assay are as follows: 100 mM HEPES (pH 7.5), 10 mM MgCl₂, 1 mM dithiothreitol (DTT), 0.01% BSA, 0.25 nM JAK3, 0.25 mg/ml polyE4Y, and 5 μM ³³P-γ-ATP (200 µCi/µmol). A 10 mM stock solution of VX-509 is prepared in DMSO, from which additional dilutions are prepared. A substrate mixture (100 mM HEPES, 10 mM MgCl₂, 0.5 mg/ml polyE4Y, and 10 μM ³³P-γ-ATP) is added and mixed with VX-509 stock solution. The reaction is initiated by the addition of an enzyme mixture [100 mM HEPES (pH 7.5), 10 mM MgCl2, 2 mM DTT, 0.02% BSA, 0.5 nM JAK3]. After 15 minutes, the reaction was quenched with 20% trichloroacetic acid (TCA). The quenched reaction was transferred to the GF/B filter plates and washed three times with 5% TCA. Following the addition of Ultimate Gold scintillant (50 μl), the samples were counted in a Packard TopCount gamma counter (PerkinElmer). In this procedure, the radioactivity trapped is a measure of the residual JAK3 kinase activity. From the activity versus concentration of VX-509 titration curve, the Ki value was determined by fitting the data to an equation for competitive tight binding inhibition kinetics using Prism software.
細胞アッセイ	細胞株	Human B cells
	濃度	~1 μM
	反応時間	6 d
	実験の流れ	Frozen purified human B cells atr thawed, washed, and resuspended in complete medium. Cells are plated onto a 96-well plate at a density of 2 × 10⁵ cells/well. VX-509 is added, and plates are incubated for 30 minutes at 37°C, followed by stimulation with a combination of 10 ng/ml IL-4 and 1 μg/ml CD40L. DMSO alone is added to the top two rows, one of which is stimulated with IL-4 or CD40L (negative control) and the other of which served as a proliferation control. The plates are incubated at 37°C for 6 days. On day 6, cells are pulsed with [3H]thymidine for 7 hours and harvested onto filters for radioactive determination using a PerkinElmer-Wallace beta counter (1205 Betaplate Beta Liquid Scintillation Counter). Data are analyzed with Softmax pro software to generate an IC50 value.
動物実験	動物モデル	Collagen-induced arthritis (CIA) rat model
	投薬量	50 mg/kg q.d.
	投与方法	p.o.

参考

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：

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection [ Antimicrob Agents Chemother, 2024, 68(4):e0135023.]	PubMed: 38470034
An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1 [ Br J Cancer, 2023, 10.1038/s41416-023-02196-z]	PubMed: 36810913
Okadaic Acid Activates JAK/STAT Signaling to Affect Xenobiotic Metabolism in HepaRG Cells [ Cells, 2023, 12(5)770]	PubMed: 36899906
Megakaryopoiesis impairment through acute innate immune signaling activation by azacitidine [ J Exp Med, 2022, 219(11)e20212228]	PubMed: 36053753
PDGF-D-PDGFRβ signaling enhances IL-15-mediated human natural killer cell survival [ Proc Natl Acad Sci U S A, 2022, 119(3)e2114134119]	PubMed: 35027451
Topical VX-509 attenuates psoriatic inflammation through the STAT3/FABP5 pathway in keratinocytes [ Pharmacol Res, 2022, 182:106318]	PubMed: 35728766
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7]	PubMed: 34997030
Selective inhibition of JAK3 signaling is sufficient to reverse alopecia areata [ JCI Insight, 2021, 6(7)142205]	PubMed: 33830087
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004]	PubMed: 31740922
CTRP9 induces iNOS expression through JAK2/STAT3 pathway in Raw 264.7 and peritoneal macrophages. [ Biochem Biophys Res Commun, 2020, 523(1):98-104]	PubMed: 31837806

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。

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