.gif)
In vitro: In cell lines from multiple solid tumor lineages, combination treatment with ACY-241 and paclitaxel enhances inhibition of proliferation and increases cell death relative to either single agent alone. Combination treatment with ACY-241 and paclitaxel also results in more frequent occurrence of mitotic cells with abnormal multipolar spindles and aberrant mitoses, and is associated with increased frequency of abnormal multipolar mitotic spindle formation, induction of aneuploidy, and increased cell death. In A2780 ovarian cancer cells, 24 hour treatment with 300 nM ACY-241 results in increased hyperacetylation of α-tubulin, consistent with inhibition of the tubulin deacetylase HDAC6. Low exposures of ACY-241 result in selective inhibition of HDAC6, while higher exposures lead to inhibition of Class I HDAC isozymes. In vivo: ACY-241 has a favourable safety profile than non-selective pan-HDAC inhibitors. It has the potential for a substantially reduced side effect profile versus current nonselective HDAC inhibitor drug candidates due to reduced potency against Class I HDACs while retaining the potential for anticancer effectiveness.
| Cell Experiment | |
|---|---|
| Cell lines | A2780 ovarian cancer cells |
| Preparation method | A2780 cells are cultured with vehicle or a range of ACY-241 concentrations for 24 hours prior to immunoblotting. |
| Concentrations | 0.1, 0.3, 0.5, 1, 3 μM |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | Female athymic nude mice (Crl:NU(NCr)-Foxn1nu) |
| Formulation | |
| Dosages | 50 mg/kg |
| Administration | i.p. |
| Molecular Weight | 467.95 |
| Formula | C24H26ClN5O3 |
| CAS Number | 1316215-12-9 |
| Solubility (25°C) | 93 mg/mL in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| 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.
| Related HDAC Products |
|---|
| Ac-Arg-Gly-Lys(Ac)-AMC
Ac-Arg-Gly-Lys(Ac)-AMC is a substrate for HDAC. |
| Chlamydocin
Chlamydocin, a fungal metabolite, is a highly potent HDAC inhibitor, with an IC50 of 1.3 nM. |
| HDAC-IN-30
HDAC-IN-30 is a novel multi-target HDAC inhibitor, including HDAC1 (IC50=13.4 nM),HDAC2 (IC50=28.0 nM), HDAC3 (IC50=9.18 nM), HDAC6 (IC50=42.7 nM), HDAC8 (IC50=131 nM). |
| Ac-Arg-Gly-Lys(Ac)-AMC acetate
Ac-Arg-Gly-Lys(Ac)-AMC acetate is a substrate for histone deacetylase (HDAC) and can be used in a novel fluorescent assay for HDAC activity. |
| JPS014 TFA
JPS014 TFA is a benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTAC). |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.
