Uses
PCI-24781 is a novel hydroxamic acid HDAC inhibitor (histone deacetylase inhibitor). PCI-24781 exerts cytotoxicity and histone H3 alterations via caspase-8 and FADD in leukemia cells.
Definition
ChEBI: 3-[(dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)-oxomethyl]phenoxy]ethyl]-2-benzofurancarboxamide is a member of benzofurans.
Biological Activity
cra-024781 is a novel hdac inhibitor targeting hdac1, hdac2, hadc3, hadc6, hadc8, hadc10 with ic50 value of 7 nm(ki), 19 nm(ki), 8.2 nm(ki), 17 nm(ki), 280 nm(ki), 24 nm(ki), respectively [1].histone deacetylases (hdac) are a class of enzymes that remove acetyl groups (o=c-ch3) from an ε-n-acetyl lysine amino acid on a histone, allowing the histones to wrap the dna more tightly.cra-024781 exhibits potent antitumor activity against ten human tumor cell lines with gi50 ranging from 0.15 μm to 3.09 μm. cra-024781 also has an antiproliferative effect on huvec endothelial cells with gi50 of 0.43 μm. cra-024781 treatment causes dose-dependent accumulation of both acetylated histones and acetylated tubulin in hct116 or dld-1 cells suggesting that hdac enzymes are inhibited in these cells. cra-024781 also induces the expression of p21 (a protein playing a role in the antitumor effect) and leads to parp cleavage and accumulation of the γh2ax, which indicate apoptosis [1].treatment with cra-024781 at 200 mg/kg once daily every other day significantly inhibits the growth of hct116 and dld-1 xenografts in mice by 69% and 59%, respectively. in the hct116 model, treatment with cra-024781 at 20 mg/kg, 40 mg/kg, 80 mg/kg, or 160 mg/kg (q.d. × 4 per week) causes inhibition of tumor growth by 48%, 57%, 82.2%, or 80.0%, respectively [1].
Enzyme inhibitor
This broad-spectrum histone deacetylase inhibitor (FW = 394.48 g/mol; CASs = 783355-60-2, 783356-67-2 (HCl)); Solubility: 80 mg/mL DMSO; <1 mg/mL Water; Formulated in 30% HP-cyclodextrin in water), also known as CRA-024781 and systematically as 3-((dimethylamino)methyl)- N-(2-(4-(hydroxycarbamoyl)phenoxy)ethyl)benzofuran-2-carboxamide, is a novel broad-spectrum HDAC inhibitor targeting HDAC1, HDAC2, HDAC3, HDAC6, HDAC8 and HDAC10 with Ki of 7 nM, 19 nM, 8.2 nM, 17 nM, 280 nM, 24 nM, respectively. PCI-24781 treatment causes dosedependent accumulation of both acetylated histones and acetylated tubulin in HCT116 or DLD-1 cells. It also induces expression of p21 and leads to PARP cleavage and accumulation of the γH2AX.
References
[1]. buggy jj, cao za, bass ke, et al. cra-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. mol cancer ther, 2006, 5(5): 1309-1317..
