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.
|Cell lines||Ba/F3-EpoR-JAK2V617F or HEL cells|
|Preparation method||Cells were seeded at 2000/well of white bottom 96-well plates, treated with compounds from DMSO stocks (0.2% final DMSO concentration), and incubated for 48 hours at 37°C with 5% CO2. Viability was measured by cellular ATP determination using the Cell-Titer Glo (Promega) luciferase reagent or viable cell counting. Values were transformed to percent inhibition relative to vehicle control, and IC50 curves were fitted according to nonlinear regression analysis of the data using PRISM GraphPad.|
|Animal models||6- to 8-week-old female BALB/c mice Ba/F3-JAK2V617F cells model|
|Formulation||5% dimethyl acetamide, 0.5% methocellulose|
|Dosages||180mg/kg, twice a day|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 50 mg/mL|
|Source||Blood cancer journal (2016) . Figure 4. ruxolitinib (Abmole Bioscience, Houston, TX, USA) and fedratinib (Abmole Bioscience)|
|Cell Lines||Embroys of wild-type zebrafish|
|Concentrations||1 μM ~ 8 μM|
|Incubation Time||24 h|
|Results||The expression of CALRdel52 mRNA significantly increased stat5 phosphorylation (Figure 4a, lane 2). Furthermore, treatment with ruxolitinib and fedratinib significantly ameliorated the enhanced stat5 phosphorylation induced by CALR-del52 mRNA (Figure 4a, lane 3 and 4). In addition, treatment with ruxolitinib significantly decreased the numbers of CD41+ thrombocytes in uninjected control as well as CALR-del52-injected embryos in a dose-dependent manner (Figure 4b). Whereas treatment with fedratinib only had minimal inhibitory effect on the number of CD41+ thrombocytes in uninjected control embryos, and had a modest and significant dose-independent inhibitory effect on mutant CALR-induced thrombocytosis (Figure 4c). Our results demonstrated that mutant CALR-mediated pathogenic thrombopoiesis involves jak-stat activation that can be blocked by JAK inhibitors.|
|Source||Nature (2014). Figure 1. The JAK inhibitor INCB018424 (S-ruxolitinib, Abmole Bioscience)|
|Method||automated blood counter, flowcytometry|
|Cell Lines||haematopoietic cell and BM MSCs|
|Concentrations||oral gavage (30mg/kg, twice per day separated 10–12h)|
|Incubation Time||4 weeks|
|Results||Nestin1 MSC reduction was instead explained by a threefold increased apoptotic rate in mutant mice, and was not prevented by the JAK inhibitor ruxolitinib. Treatment with the JAK1/2 inhibitor ruxolitinib reduces haematopoietic cell expansion in MPN but it does not rescue BM MSCs.|
Blood Cancer J. 2016 Oct 7;6(10):e481.
Expression of CALR mutants causes mpl-dependent thrombocytosis in zebrafish.
S-Ruxolitinib purchased from AbMole
Nature. 2014 Aug 7;512(7512):78-81.
Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms.
S-Ruxolitinib purchased from AbMole
|Related JAK Products|
Ruxolitinib phosphate(INCB018424 phosphate) 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.
Oclacitinib is a novel inhibitor of JAK family members with IC50 ranging from 10 to 99 nM and JAK1-dependent cytokines with IC50 ranging from 36 to 249 nM, which did not inhibit a panel of 38 non-JAK kinases.
Baricitinib phosphate(INCB 028050; LY 3009104) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2.
Janex-1 is a cell-permeable, reversible, potent, ATP-competitive, and specific inhibitor of JAK3 (IC50 = 78 μM); has no effect on JAK1, JAK2, or Zap/Syk or SRC tyrosine kinases.
Decernotinib is a potent and selective Janus kinase 3 (JAK3) inhibitor with Ki of 2.5 nM; IC50 is 50-170 nM in cellular assays.
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