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Description: Baricitinib phosphate, the phosphate salt of Baricitinib which is also known as LY3009104 or INCB028050 or trade name Olumiant, is a potent, selective, ATP competitive and orally bioavailable inhibitor of tyrosine-protein kinase JAK1 or JAK2. It is an FDA approved drug for the treatment of rheumatoid arthritis (RA) in the United States. In vitro, it is able to inhibit JAK1 and JAK2 with IC50 values in the low nanomolar range of 5.9 and 5.7 nM, respectively, while it displays low inhibitory activity for JAK3 and moderate activity for TYK2. Baricitinib inhibits intracellular signaling of several proinflammatory cytokines such as IL-6 and IL-23 at concentrations<50 nM. JAK signaling is central to a number of fundamental processes including the generation of RBCs.
References: J Immunol. 2010 May 1;184(9):5298-307; Curr Opin Pharmacol. 2012 Aug;12(4):464-70.
Related CAS: 1187594-09-7 (free base) 1187595-84-1 (phosphate)
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: 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.
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 INCB018424 concentration required for inhibition of 50% of the fluorescent signal.
Cell Assay: Cells (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.
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.
Purity ≥98%
COA
MSDS
NMR
HPLC
Cellular activity of INCB028050. J Immunol. 2010 May 1;184(9):5298-307.
Anti-inflammatory and DMARD activity of once daily INCB028050 in rats with established disease in the adjuvant arthritis model. J Immunol. 2010 May 1;184(9):5298-307.
Suppression of delayed-type hypersensitivity by INCB028050. J Immunol. 2010 May 1;184(9):5298-307.
INCB028050 is efficacious and well tolerated independently of effects on humoral immunity. J Immunol. 2010 May 1;184(9):5298-307.
INCB028050 improves clinical and histologic signs of disease in the murine CIA model.