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Decernotinib (VX-509) JAK inhibitor

Name: Decernotinib (VX-509)
Brand: Selleck Chemicals
SKU: S7541
Availability: InStock
Rating: 5 (11 reviews)

Cat.No.S7541

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

Chemical Structure

Molecular Weight: 392.38

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.86%

99.86

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Chemical Information, Storage & Stability

Molecular Weight	392.38	Formula	C₁₈H₁₉F₃N₆O	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	944842-54-0	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CCC(C)(C(=O)NCC(F)(F)F)NC1=NC(=NC=C1)C2=CNC3=C2C=CC=N3

Solubility

In vitro
Batch:

DMSO : 78 mg/mL ( (198.78 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 78 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.9mg/ml (9.94mM)	Taking the 1 mL working solution as an example, add 50 μL of 78 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.55mg/ml (1.40mM)	Taking the 1 mL working solution as an example, add 50 μL of 11 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	JAK3 ^[1] 2.5 nM(Ki) JAK1 ^[1] 11 nM JAK1 ^[1] 11 nM(Ki) JAK2 ^[1] 13 nM(Ki) TYK2 ^[1] 13 nM(Ki)
In vitro	In HT-2 cells, Decernotinib (VX-509) inhibits IL-2–stimulated HT-2 STAT-5 phosphorylation, human T-cell blast proliferation, and CD40L/IL-4–induced B-cell proliferation. ^[1]
Kinase Assay	Kinase Activity Assays
Kinase Assay	The effect of Decernotinib (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 this compound 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 it. 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.
In vivo	In a rat model of collagen-induced arthritis, S7541 (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, S7541 (50 mg/kg, p.o.) significantly suppresses ear edema. ^[1] In a rat HvG model, S7541 (50 mg/kg, p.o.) results in dose-dependent inhibition of popletial lymph node (PLN) hyperplasia. ^[2]
References	https://pubmed.ncbi.nlm.nih.gov/25762693/ https://pubmed.ncbi.nlm.nih.gov/26230873/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01886209	Completed	Drug Interactions	Vertex Pharmaceuticals Incorporated	June 2013	Phase 1
NCT01830985	Completed	Rheumatoid Arthritis	Vertex Pharmaceuticals Incorporated	April 2013	Phase 2\|Phase 3
NCT01754935	Completed	Rheumatoid Arthritis	Vertex Pharmaceuticals Incorporated	January 2013	Phase 2
NCT01052194	Completed	Rheumatoid Arthritis	Vertex Pharmaceuticals Incorporated	February 2010	Phase 2

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