Decernotinib (VX-509)

For research use only. Not for use in humans.

Catalog No.S7541

Decernotinib (VX-509) Chemical Structure

Molecular Weight(MW): 392.38

Decernotinib (VX-509) is a potent and selective JAK3 inhibitor with Ki of 2.5 nM, >4-fold selectivity over JAK1, JAK2, and TYK2, respectively. Phase 2/3.

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Biological Activity

Description Decernotinib (VX-509) is a potent and selective JAK3 inhibitor with Ki of 2.5 nM, >4-fold selectivity over JAK1, JAK2, and TYK2, respectively. Phase 2/3.
JAK3 [1] JAK1 [1] JAK1 [1] JAK2 [1] TYK2 [1]
2.5 nM(Ki) 11 nM 11 nM(Ki) 13 nM(Ki) 13 nM(Ki)
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]


Kinase Assay:[1]
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Kinase Activity Assays:

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 Research:[1]
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  • Cell lines: Human B cells
  • Concentrations: ~1 μM
  • Incubation Time: 6 d
  • Method: 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.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Collagen-induced arthritis (CIA) rat model
  • Formulation: 10% vitamin E d-α-tocophenyl polyethylene glycol 1000 succinate and 1% hydroxypropyl methylcellulose acetyl succinate
  • Dosages: 50 mg/kg q.d.
  • Administration: p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 78 mg/mL (198.78 mM)
Ethanol 20 mg/mL warmed (50.97 mM)
Water 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.

Chemical Information

Molecular Weight 392.38


CAS No. 944842-54-0
Storage powder
in solvent
Synonyms N/A
Smiles CCC(C)(NC1=NC(=NC=C1)C2=C[NH]C3=NC=CC=C23)C(=O)NCC(F)(F)F

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID