Decernotinib (VX-509)

Catalog No.S7541

For research use only.

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.

Decernotinib (VX-509) Chemical Structure

CAS No. 944842-54-0

Selleck's Decernotinib (VX-509) has been cited by 7 Publications

Purity & Quality Control

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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.
Targets
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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]
  • 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.
Animal Research:[1]
  • Animal Models: Collagen-induced arthritis (CIA) rat model
  • Dosages: 50 mg/kg q.d.
  • Administration: p.o.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 392.38
Formula

C18H19F3N6O

CAS No. 944842-54-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CCC(C)(C(=O)NCC(F)(F)F)NC1=NC(=NC=C1)C2=CNC3=C2C=CC=N3

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01886209 Completed Drug: Prednisone|Drug: VX-509|Drug: Methylprednisolone Drug Interactions Vertex Pharmaceuticals Incorporated June 2013 Phase 1
NCT01830985 Completed Drug: VX-509 Rheumatoid Arthritis Vertex Pharmaceuticals Incorporated April 2013 Phase 2|Phase 3
NCT01754935 Completed Drug: VX-509|Drug: VX-509 matching placebo Rheumatoid Arthritis Vertex Pharmaceuticals Incorporated January 2013 Phase 2
NCT01052194 Completed Drug: Placebo|Drug: VX-509 Rheumatoid Arthritis Vertex Pharmaceuticals Incorporated February 2010 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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