S-Ruxolitinib (INCB018424)

Catalog No.S2902 Batch:S290201

Print

Technical Data

Formula

C17H18N6
Molecular Weight 306.37 CAS No. 941685-37-6
Solubility (25°C)* In vitro DMSO 61 mg/mL (199.1 mM)
Ethanol 61 mg/mL (199.1 mM)
Water 5 mg/mL (16.32 mM)
* <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 S-Ruxolitinib is the chirality of INCB018424, which is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM, >130-fold selectivity for JAK1/2 versus JAK3. Phase 3.
Targets
JAK2 [1]
(Cell-free assay)		 JAK1 [1]
(Cell-free assay)		 TYK2 [1]
(Cell-free assay)
2.8 nM 3.3 nM 19 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

Selleck's S-Ruxolitinib (INCB018424) has been cited by 25 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
Guizhi Fuling capsule relieves memory deficits by inhibition of microglial neuroinflammation through blocking JAK2/STAT3 pathway in presenilin1/2 conditional double knockout mice [ Front Immunol, 2023, 14:1185570] PubMed: 37465679
Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways [ Int Immunopharmacol, 2023, 118:109993] PubMed: 36931170
Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways [ Int Immunopharmacol, 2023, 118:109993] PubMed: 36931170
Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways [ International Immunopharmacology, 2023, Volume 118] PubMed: None
Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies [ NPJ Precis Oncol, 2022, 6(1):75] PubMed: 36274097
Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2022, 14(21)5215] PubMed: 36358633
ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation [ Nat Commun, 2021, 12(1):2346] PubMed: 33879767
Long-term adaptation following influenza A virus host shifts results in increased within-host viral fitness due to higher replication rates, broader dissemination within the respiratory epithelium and reduced tissue damage [ PLoS Pathog, 2021, 17(12):e1010174] PubMed: 34919598
A Single-Cell Landscape of High-Grade Serous Ovarian Cancer [ Nat Med, 2020, 10.1038/s41591-020-0926-0] PubMed: 32572264

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.