INCB18424 (Ruxolitinib), the most advanced JAK-1 and JAK-2 inhibitor, is in Phase III testing to treat myelofibrosis. INCB18424 demonstrated potent in vitro cellular activity (100-130 nM) in an engineered Ba/F3 cell line harboring the JAK2V617F mutation and EPO-independent erythroid colony growth of precursor cells from PV patients (IC50 of 67 nM) while showing lesser effect on normal colony formation from healthy donors (IC50 > 400 nM).
BMC Biol. 2021 May 20;19(1):108.
Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans
INCB18424 purchased from AbMole
Blood Adv. 2020 Jul 14;4(13):3000-3010.
Inflammation-driven activation of JAK/STAT signaling reversibly accelerates acute myeloid leukemia in vitro
INCB18424 purchased from AbMole
J Virol. 2020 Feb 14;94(5):e01791-19.
|Source||Leukemia (2013). Figure 2. INCB18424|
|Cell Lines||leukemia cells|
|Incubation Time||48 h|
|Results||INCB18424 showed a significantly better inhibitory effect than TG101209 at concentrations below 1 μM. Both inhibitors also promoted apoptosis (Figure 2b) and delayed cell cycle progression (Figure 2c) of the AEtr leukemia cell line.|
|Source||Leukemia (2013). Figure 1. INCB18424|
|Cell Lines||AML1–ETO- and AE9a-transformed cells|
|Concentrations||150, 300, 600, 1200 nM|
|Incubation Time||36 h|
|Results||Similar to the shRNA results, both inhibitors reduced the colony-forming ability of the transformed cells in a dose-dependent manner|
|Cell lines||Ba/F3-EpoR-JAK2V617F and HEL cell lines|
|Preparation method||Cell proliferation assay. 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.|
|Concentrations||0~10 µ M|
|Incubation time||48 h|
|Animal models||myeloproliferative neoplasm mouse model|
|Formulation||5% dimethyl acetamide, 0.5% methocellulose|
|Dosages||180mg/kg began within 24 hours of cell inoculation, twice daily|
|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 Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.
|Solubility||DMSO 60 mg/mL|
Ruxolitinib as potential targeted therapy for patients with JAK2 rearrangements.
Chase A, et al. Haematologica. 2012 Aug 8. PMID: 22875628.
Biology and Clinical Management of Myeloproliferative Neoplasms and Development of the JAK Inhibitor Ruxolitinib.
Mascarenhas J, et al. Curr Med Chem. 2012 Jul 24. PMID: 22830345.
Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia.
Eghtedar A, et al. Blood. 2012 May 17;119(20):4614-8. PMID: 22422826.
JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis.
Harrison C, et al. N Engl J Med. 2012 Mar 1;366(9):787-98. PMID: 22375970.
|Related JAK Products|
Delgocitinib, also known as LEO-124249 and JTE052, is a potent and selective JAK inhibitor with IC50 values of 2.8, 2.6, 13 and 58 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.
PF-06700841 is a potent dual Janus kinase 1 (JAK1) and TYK2 inhibitor with IC50s of 17 nM and 23 nM, respectively. PF-06700841 also inhibits JAK2 and JAK3 with IC50s of 77 nM and 6.49 μM, respectively.
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.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.