Droxinostat (NS-41080) is a selective HDAC inhibitor with IC50 of 16.9, 2.47 and 1.46 uM for HDAC3, HDAC6 and HDAC8, respectively; does not inhibit HDAC1, HDAC2, HDAC4, HDAC5, HDAC7, HDAC9, and HDAC10 with IC50 of >20 uM; sensitizes malignant cells to death receptor ligands FAS and TRAIL sensitization with IC50 of 20 and 39 uM, respectively; decreases the expression of the caspase-8 inhibitor FLIP, downregulates c-FLIP(L) and c-FLIP(S) mRNA and protein levels, causes PARP degradation, reduces cell survival, and induces apoptosis in MCF-7 breast cancer cells.
Images & Validation
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Key Properties
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CAS Number
99873-43-5
MW
243.7
Purity
>98% (HPLC)
Formula
C11H14ClNO3
SMILES
O=C(NO)CCCOC1=CC=C(Cl)C=C1C
Target
HDAC
Solubility
10 mM in DMSO
Bioactivity
−
In Vitro
Droxinostat selectively inhibits HDAC3, HDAC6, and HDAC8 with IC50 values of 16.9 μM, 2.47 μM, and 1.46 μM, respectively. Droxinostat (0, 10, 20, or 40 μM; 48 h) suppresses HDAC3 expression and induces acetylation of histones H3 and H4.Droxinostat (0, 10, 20, 40, and 80 μM; 0, 24, 48, 72, 96, and 120 h) inhibits cell proliferation and colony formation in HepG2 and SMMC-7721 cells. Droxinostat (0 to 80 μM; 48 h) induces hepatoma cell apoptosis by activating mitochondrial apoptotic pathways and downregulating FLIP. Western blot analysis. Cell line: SMMC-7721 and HepG2 (Human liver carcinoma cell lines). Concentration: 0, 10, 20, or 40 μM. Incubation time: 48 h. Result: Significantly decreased the expression of HDAC3 with dose-dependent in HepG2 and SMMC-7721 cell lines. Significantly enhanced the expression of acetyl-H3 (Ac-H3) and acetylH4 (Ac-H4) in HepG2 and SMMC-7721 cells in a dose-dependent manner. Upregulated the levels of phospho-p53 and cleaved caspase 3 protein and downregulated the levels of Bcl-2.Markedly increased the Bax/Bcl-2 ratio in a dose-dependent manner and increased the expression of cleaved PARP protein in HepG2 cells in a dose-dependent manner. Significant reduced the FLIP expression and enhanced caspase 8 activity in both HepG2 and SMMC-7721cell. Cell Proliferation Assay Cell line: SMMC-7721 and HepG2. Concentration: 0, 10, 20, 40, and 80 μM. Incubation time: 0, 24, 48, 72, 96, and 120 h. Result: Decreased the viability with a time-and dose-dependent in both cell lines. Apoptosis Analysis Cell line: SMMC-7721 and HepG2. Concentration: 0 to 80 μM. Incubation time: 48 h. Result: Clearly led to dose-dependent apoptosis, but did not induce hepatoma cell apoptosis at 10 μM and had an apoptotic effect at a starting concentration of 20 μM. RT-PCR Cell line: SMMC-7721 and HepG2. Concentration: 20 μM and 40 μM. Incubation time: 48 h. Result: Significantly increased the mRNA levels of Bax and p53 genes associated with the mitochondrial p53 apoptosis pathway in a dose-dependent manner in HepG2 and SMMC-7721 cells. Significantly increased the Bcl-2 mRNA levels in SMMC-7721 cells at a concentration of 40 uM and also increased the Bax/Bcl-2 mRNA ratio.
25 mg, 100 mg, 50 mg, 1 ml x 10 mM (in DMSO), 200 mg
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