AR-42 is a novel HDAC inhibitor with an IC50 of 0.61 μM for acute lymphoblastic leukemia (697) cell lines. In chronic lymphocytic leukemia (CLL) cells, the 48-hr LC50 of AR-42 is 0.76 μM. AR-42 produces dose- and time-dependent acetylation both of histones and tubulin, and induces caspase-dependent apoptosis that is not reduced in the presence of stromal cells. AR-42 significantly reduced leukocyte counts and/or prolonged survival in three separate mouse models of B-cell malignancy without evidence of toxicity. AR-42 has in vitro and in vivo efficacy at tolerable doses. In additon, AR-42 promoted hyperacetylation of H3, H4, and alpha-tubulin, and up-regulation of p21. Down-regulation of Kit occurred after AR-42 爐reatment via inhibition of Kit transcription.
|Preparation method||Cells are exposed to varous concentrations of AR-42 for 96 hours. The medium is removed and replaced by 150 μL of 0.5 mg/mL of MTT in RPMI 1640 medium, and the cells are incubated in the CO2 incubator at 37 °C for 2 hours. Supernatants are removed from the wells, and the reduced MTT dye is solubilized with 200 μL/well of DMSO. Absorbance is determined on a plate reader at 570 nm.|
|Concentrations||Dissolved in DMSO, final concentrations ~2.5 μM|
|Incubation time||96 hours|
|Animal models||Intact male NCr athymic nude mice inoculated s.c. with PC-3 cells|
|Formulation||Formulated in methylcellulose/Tween 80|
|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 60 mg/mL|
|Related HDAC Products|
WT-161 is a potent and selective HDAC6 inhibitor with an IC50 of 0.40 nM.
EDO-S101 is a pan HDAC inhibitor; inhibits HDAC1, HDAC2 and HDAC3 with IC50 values of 9, 9 and 25 nM, respectively.
Citarinostat (ACY-241) is an orally available selective HDAC6 inhibitor with IC50 of 2.6 nM and 46 nM for HDAC6 and HDAC3, respectively. It has 13 to 18-fold selectivity towards HDAC6 in comparison to HDAC1-3.
BRD73954 ia a potent and selective HDAC inhibitor with IC50 of 36 nM and 120 nM for HDAC6 and HDAC8, respectively.
Sodium butyrate is the sodium salt of butyric acid, which has been reported to cause hyperacetylation of histones due to its role as a HDAC inhibitor with IC50 values of 0.3, 0.4, 0.3 mM for HDAC1, 2 and 7 respectively.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.