Ruxolitinib

Catalog No.S1378 Batch:S137821

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Technical Data

Formula

C17H18N6
Molecular Weight 306.37 CAS No. 941678-49-5
Solubility (25°C)* In vitro DMSO 61 mg/mL (199.1 mM)
Ethanol 12 mg/mL (39.16 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 95% Corn oil
3.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 60 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. 
Clear solution
5%DMSO 40%PEG 300 5%Tween80 50% ddH2O
3.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 60 mg/mL clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween-80 to the above system, mix evenly to clarify it; then continue Add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Ruxolitinib is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib kills tumor cells through toxic mitophagy. Ruxolitinib induces autophagy and enhances apoptosis.
Targets
JAK2 [1]
(Cell-free assay)		 JAK1 [1]
(Cell-free assay)
2.8 nM 3.3 nM
In vitro INCB018424 potently and selectively inhibits JAK2V617F-mediated signaling and proliferation in Ba/F3 cells and HEL cells. INCB018424 markedly increases apoptosis in a dose dependent manner in Ba/F3 cells. INCB018424 (64 nM) results in a doubling of cells with depolarized mitochondria in Ba/F3 cells. INCB018424 inhibits proliferating of erythroid progenitors from normal donors and polycythemia vera patients with IC50 of 407 nM and 223 nM, respectively. INCB018424 demonstrates remarkable potency against erythroid colony formation with IC50 of 67nM. [1]
In vivo INCB018424 (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. INCB018424 (180 mg/kg, orally, twice a day) markedly reduces splenomegaly and circulating levels of inflammatory cytokines, and preferentially eliminated neoplastic cells, resulting in significantly prolonged survival without myelosuppressive or immunosuppressive effects in a JAK2V617F-driven mouse model. [1] The primary end point is reached in 41.9% of patients in the Ruxolitinib group as compared with 0.7% in the placebo group in the double-blind trial of myelofibrosis. Ruxolitinib results in maintaining of reduction in spleen volume and improvement of 50% or more in the total symptom score. [2] A total of 28% of the patients in the Ruxolitinib (15 mg twice daily) group has at least a 35% reduction in spleen volume at week 48 in patients with myelofibrosis, as compared with 0% in the group receiving the best available therapy. The mean palpable spleen length has decreased by 56% with Ruxolitinib but has increased by 4% with the best available therapy at week 48. Patients in the ruxolitinib group has an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis. [3]

Protocol (from reference)

Kinase Assay:[1]
  • Binding assay

    Recombinant proteins are expressed using Sf21 cells and baculovirus vectors and purified with affinity chromatography. JAK kinase assays use a homogeneous time-resolved fluorescence assay with the peptide substrate (-EQEDEPEGDYFEWLE). Each enzyme reaction is carried out with Ruxolitinib or control, JAK enzyme, 500 nM peptide, adenosine triphosphate (ATP; 1mM), and 2% dimethyl sulfoxide (DMSO) for 1 hour. The 50% inhibitory concentration (IC50) is calculated as INCB018424 concentration required for inhibition of 50% of the fluorescent signal.
Cell Assay:[1]
  • Cell lines

    Ba/F3 and HEL cells

  • Concentrations

    3 μM

  • Incubation Time

    48 hours

  • Method

    Cells are seeded at 2 × 103/well of white bottom 96-well plates, treated with INCB018424 from DMSO stocks (0.2% final DMSO concentration), and incubated for 48 hours at 37 ℃ with 5% CO2. Viability is measured by cellular ATP determination using the Cell-Titer Glo luciferase reagent or viable cell counting. Values are transformed to percent inhibition relative to vehicle control, and IC50 curves are fitted according to nonlinear regression analysis of the data using PRISM GraphPad.
Animal Study:[1]
  • Animal Models

    JAK2V617F-driven mouse model

  • Dosages

    180 mg/kg

  • Administration

    Oral gavage

Customer Product Validation

Data from [Data independently produced by Blood, 2014, 123(24), 3832-42]

Data from [Data independently produced by Gene Ther, 2014, 10.1038/gt.2014.83]

Data from [Data independently produced by J Immunol, 2012, 189(6), 2784-92]

, , Yong Weon Yi Georgetown University

Selleck's Ruxolitinib has been cited by 646 publications

Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer [ Nat Commun, 2024, 15(1):2503] PubMed: 38509064
Inhibition of neutrophil swarming by type I interferon promotes intracellular bacterial evasion [ Nat Commun, 2024, 15(1):8663] PubMed: 39375351
Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms [ Nat Commun, 2024, 15(1):2989] PubMed: 38582902
Defective N-glycosylation of IL6 induces metastasis and tyrosine kinase inhibitor resistance in lung cancer [ Nat Commun, 2024, 15(1):7885] PubMed: 39251588
Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients [ Acta Neuropathol, 2024, 147(1):28] PubMed: 38305941
Tumor cell senescence-induced macrophage CD73 expression is a critical metabolic immune checkpoint in the aging tumor microenvironment [ Theranostics, 2024, 14(3):1224-1240] PubMed: 38323313
JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors [ J Exp Clin Cancer Res, 2024, 43(1):64] PubMed: 38424636
A novel strategy to generate immunocytokines with activity-on-demand using small molecule inhibitors [ EMBO Mol Med, 2024, 16(4):904-926] PubMed: 38448543
Somatic PDGFRB activating variants promote smooth muscle cell phenotype modulation in intracranial fusiform aneurysm [ J Biomed Sci, 2024, 31(1):51] PubMed: 38741091
Somatic PDGFRB activating variants promote smooth muscle cell phenotype modulation in intracranial fusiform aneurysm [ J Biomed Sci, 2024, 31(1):51] PubMed: 38741091

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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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