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.
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
|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.|
|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 51 mg/mL|
|Related JAK Products|
Delphinidin (chloride) is an anthocyanidin, a natural plant pigment which can modulate JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells.
AZD4205 is a novel potent and selective janus kinase 1 (JAK1) inhibitor, with IC50 value of 73 nM.
PF-06826647, also known as Tyk2-IN-8, is a selective and orally administered tyrosine kinase 2 (TYK2) inhibitor, with IC50 of 17 nM.
PF-06700841 (Brepocitinib) tosylate is a dual inhibitor of JAK1 and TYK2, with IC50 values of 17 nM and 23 nM, respectively.
|JAK3-IN-6 (Compound 2)
JAK3-IN-6 (Compound 2) CAS#: 1443235-95-7 is a potent and highly selective JAK3 inhibitor, with an IC50 of 0.15 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.