Decernotinib (VX-509)

Catalog No.S7541 Batch:S754102

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Technical Data

Formula

C18H19F3N6O
Molecular Weight 392.38 CAS No. 944842-54-0
Solubility (25°C)* In vitro DMSO 78 mg/mL (198.78 mM)
Ethanol 78 mg/mL (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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 Assay:[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 Study:[1]
  • Animal Models

    Collagen-induced arthritis (CIA) rat model

  • Dosages

    50 mg/kg q.d.

  • Administration

    p.o.

Selleck's Decernotinib (VX-509) has been cited by 11 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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