Ruxolitinib Phosphate (INC-424, INCB-18424, INCB-018424, Jakafi and Jakavi)

Alias: INCB-018424 phosphate, INCB 018424, INCB018424; INC424, INC424, INC-424; INCB18424, INCB 18424, INCB-18424; Jakafi and Jakavi (trade name)
Cat No.:V0076 Purity: ≥98%
Ruxolitinib Phosphate (Jakafi and Jakavi), the phosphate salt of ruxolitinib which isalso known as INC424, INCB18424 or INCB018424, is a first-in class, potent, selective, and orally bioavailable JAK1/2 (Janus-associated kinase) inhibitor with IC50 of 3.3 nM/2.8 nM in cell-free assays, it exhibits >130-fold selectivity for JAK1/2 versus JAK3.
Ruxolitinib Phosphate (INC-424, INCB-18424, INCB-018424, Jakafi and Jakavi) Chemical Structure CAS No.: 1092939-17-7
Product category: JAK
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
25mg
50mg
100mg
250mg
500mg
1g
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Other Forms of Ruxolitinib Phosphate (INC-424, INCB-18424, INCB-018424, Jakafi and Jakavi):

  • Ruxolitinib (INCB-018424; INC-424)
  • S-Ruxolitinib (INCB-018424)
  • Ruxolitinib sulfate (INC 424, INCB 18424, INCB 018424, Jakafi, Jakavi)
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Purity & Quality Control Documentation

Purity: ≥98%

Purity: ≥98%

Purity: ≥98%

Purity: ≥98%

Product Description

Ruxolitinib Phosphate (Jakafi and Jakavi), the phosphate salt of ruxolitinib which is also known as INC424, INCB18424 or INCB018424, is a first-in class, potent, selective, and orally bioavailable JAK1/2 (Janus-associated kinase) inhibitor with IC50 of 3.3 nM/2.8 nM in cell-free assays, it exhibits >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib has potential antineoplastic and immunomodulating activities. It was approved in 2011 by FDA for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow, and for polycythemia vera (PCV) when there has been an inadequate response to or intolerance of hydroxyurea. It selectively binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation.

Biological Activity I Assay Protocols (From Reference)
ln Vitro

In vitro activity: Ruxolitinib (also known as INC424 and INCB18424) 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.


Kinase 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 Ruxolitinib concentration required for inhibition of 50% of the fluorescent signal.


Cell Assay: Ba/F3 and HEL 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.

ln vivo
Ruxolitinib (180 mg/kg, orally, twice a day) results in survive rate of greater than 90% by day 22 in a JAK2V617F-driven mouse model. Ruxolitinib (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. 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. 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.
Animal Protocol
Dissolved in 5% dimethyl acetamide, 0.5% methocellulose; 180 mg/kg/day; Oral gavage
JAK2V617F-driven mouse model
References
Blood.2010 Apr 15;115(15):3109-17;N Engl J Med.2012 Mar 1;366(9):799-807;N Engl J Med.2012 Mar 1;366(9):787-98.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C₁₇H₂₁N₆O₄P
Molecular Weight
404.36
CAS #
1092939-17-7
Related CAS #
Ruxolitinib;941678-49-5;Ruxolitinib (S enantiomer);941685-37-6;Ruxolitinib sulfate;1092939-16-6
SMILES
N#CC[C@H](C1CCCC1)N2N=CC(C3=C4C=CNC4=NC=N3)=C2.O=P(O)(O)O
Synonyms
INCB-018424 phosphate, INCB 018424, INCB018424; INC424, INC424, INC-424; INCB18424, INCB 18424, INCB-18424; Jakafi and Jakavi (trade name)
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 61 mg/mL (199.1 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
Solubility (In Vivo)
2% DMSO+30% PEG 300+ddH2O:5mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4730 mL 12.3652 mL 24.7304 mL
5 mM 0.4946 mL 2.4730 mL 4.9461 mL
10 mM 0.2473 mL 1.2365 mL 2.4730 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

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Biological Data
  • Ruxolitinib Phosphate

    INCB018424 (Ruxolitinib)treatment improves viability and splenomegaly in a JAK2V617F-driven model of malignant disease.Blood.2010 Apr 15;115(15):3109-17.


    Ruxolitinib Phosphate

  • Ruxolitinib Phosphate

    Macroscopic and microscopic effects of INCB018424 on spleens from mice inoculated with Ba/F3-EpoR-JAK2V617F cells.Blood.2010 Apr 15;115(15):3109-17.

  • Ruxolitinib Phosphate

    INCB018424 does not affect normal hematologic parameters.Blood.2010 Apr 15;115(15):3109-17.

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