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Decernotinib(VX-509 VRT-831509 adelatinib)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Decernotinib(VX-509 VRT-831509 adelatinib)图片
CAS NO:944842-54-0
规格:≥98%
包装与价格:
包装价格(元)
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)392.38
FormulaC18H19F3N6O
CAS No.944842-54-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 78 mg/mL (198.8 mM)
Water: <1 mg/mL
Ethanol: 20 mg/mL warmed (51.0 mM)
SMILES CodeCC[C@](NC1=NC(C2=CNC3=NC=CC=C32)=NC=C1)(C)C(NCC(F)(F)F)=O.
Synonyms

PubChem CID 59422203; VX-509; VRT831509 ; VRT-831509; VX509; VX 509 ; VRT 831509 ; Decernotinib; Adelatinib

Chemical Name: (R)-2-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide

实验参考方法
In Vitro

In vitro activity: 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.


Kinase Assay: 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.


Cell Assay: 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.

In VivoIn 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. In a rat HvG model, VX-509 (50 mg/kg, p.o.) results in dose-dependent inhibition of popletial lymph node (PLN) hyperplasia.
Animal modelCollagen-induced arthritis (CIA) rat model
Formulation & DosageDissolved in 10% vitamin E d-α-tocophenyl polyethylene glycol 1000 succinate and 1% hydroxypropyl methylcellulose acetyl succinate; 50 mg/kg; administrated orally
References

J Pharmacol Exp Ther. 2015 May;353(2):405-14; J Med Chem. 2015 Sep 24;58(18):7195-216.

生物活性


Effect of VX-509 on progression of established disease in rat CIA model. J Pharmacol Exp Ther. 2015 May;353(2):405-14.


(A) Representative histopathology photomicrographs of a control (collagen + vehicle) rat ankle and VX-509 b.i.d. treatment groups, with approximate mean score for group showing synovium (S), cartilage (large arrow), and bone (small arrow). J Pharmacol Exp Ther.2015 May;353(2):405-14.


Effect of VX-509 on the oxazolone-induced mouse DTH model. J Pharmacol Exp Ther. 2015 May;353(2):405-14.