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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.
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.
Related CAS: 941678-49-5 (free base); 941685-37-6 (S-enantiomer); 1092939-16-6 (sulfate) 1092939-17-7 (phosphate)
Product Catalog 2023
Guide to Product Handling
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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.
Lot#: V007601,Purity ≥98%
COA
MSDS
NMR
Lot#: V007602,Purity = 99.74%
Lot#: V007603,Purity ≥98%
INCB018424 (Ruxolitinib) treatment improves viability and splenomegaly in a JAK2V617F-driven model of malignant disease. Blood. 2010 Apr 15;115(15):3109-17.
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.
INCB018424 does not affect normal hematologic parameters. Blood. 2010 Apr 15;115(15):3109-17.