Citarinostat (ACY-241)

Catalog No.S8464 Synonyms: HDAC-IN-2

Citarinostat (ACY-241) Chemical Structure

Molecular Weight(MW): 467.95

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.

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Biological Activity

Description 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.
Targets
HDAC6 [1]
(Cell-free assay)
HDAC1 [1]
(Cell-free assay)
HDAC2 [1]
(Cell-free assay)
HDAC3 [1]
(Cell-free assay)
HDAC8 [1]
(Cell-free assay)
2.6 nM 35 nM 45 nM 46 nM 137 nM
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[1].

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[1].

Protocol

Cell Research:[1]
+ Expand
  • Cell lines: A2780 ovarian cancer cells
  • Concentrations: 0.1, 0.3, 0.5, 1, 3 μM
  • Incubation Time: 24 h
  • Method: A2780 cells are cultured with vehicle or a range of ACY-241 concentrations for 24 hours prior to immunoblotting.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Female athymic nude mice (Crl:NU(NCr)-Foxn1nu)
  • Formulation: --
  • Dosages: 50 mg/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

In vitro Ethanol 93 mg/mL (198.73 mM)
DMSO 41 mg/mL (87.61 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 467.95
Formula

C24H26ClN5O3

CAS No. 1316215-12-9
Storage powder
Synonyms HDAC-IN-2

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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HDAC Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID