ACY-241

Research use only, not for human use.

ACY-241, also known as Citarinostat, is a potent, selective and orally available histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity.

ACY-241, also known as Citarinostat, is a potent, selective and orally available histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity. Upon oral administration, ACY-241 inhibits the activity of HDACs; this results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibit tumor cell division and induce tumor cell apoptosis.(In Vitro):Citarinostat (ACY241; 0-3 μM; 24 hours; A2780 cells) treatment with 300 nM results in increased hyperacetylation of α-tubulin, consistent with inhibition of the tubulin deacetylase HDAC6. In contrast, hyperacetylation of histone H3, a target of Class I HDACs, is only observed at doses above 1 μM. Low exposures of Citarinostat result in selective inhibition of HDAC6, while higher exposures lead to inhibition of Class I HDAC isozymes.The single agent viability IC50 of Citarinostat (ACY241) ranged from 4.6-6.1 μM in A2780 and TOV-21G ovarian cancer and MDA-MD-231 breast cancer cells. Consistent with the viability assay, single agent Citarinostat modestly reduces proliferation at doses up to 3 μM without inducing apoptosis, while 10 μM of Citarinostat causes significant induction of apoptosis and completely suppresses proliferation.(In Vivo):Citarinostat (ACY241; 50 mg/kg; intraperitoneal injection; once daily for five days, followed by two days off; for 3 weeks; female athymic nude mice) significantly suppresses tumor growth in combination with NSC 125973.

Citarinostat (ACY241; 0-3 μM; 24 hours; A2780 cells) treatment with 300 nM results in increased hyperacetylation of α-tubulin, consistent with inhibition of the tubulin deacetylase HDAC6. In contrast, hyperacetylation of histone H3, a target of Class I HDACs, is only observed at doses above 1 μM. Low exposures of Citarinostat result in selective inhibition of HDAC6, while higher exposures lead to inhibition of Class I HDAC isozymes.The single agent viability IC50 of Citarinostat (ACY241) ranged from 4.6-6.1 μM in A2780 and TOV-21G ovarian cancer and MDA-MD-231 breast cancer cells. Consistent with the viability assay, single agent Citarinostat modestly reduces proliferation at doses up to 3 μM without inducing apoptosis, while 10 μM of Citarinostat causes significant induction of apoptosis and completely suppresses proliferation. Western Blot Analysis Cell Line:A2780 cells Concentration:0 μM, 0.1 μM, 0.3 μM, 0.5μM, 1 μM, 3 μM Incubation Time:24 hours Result:Resulted in increased hyperacetylation of α-tubulin, consistent with inhibition of the tubulin deacetylase HDAC6. In contrast, hyperacetylation of histone H3, a target of Class I HDACs, was only observed at doses above 1 μM.

Citarinostat (ACY241; 50 mg/kg; intraperitoneal injection; once daily for five days, followed by two days off; for 3 weeks; female athymic nude mice) significantly suppresses tumor growth in combination with NSC 125973. Animal Model:Female athymic nude mice (7-week-old) injected with TOV-21G cells Dosage:50 mg/kg Administration:Intraperitoneal injection; once daily for five days, followed by two days off; for 3 weeks Result:Combination treatment with NSC 125973 resulted in significantly suppression of tumor growth.

Citarinostat

Cell Cycle/DNA Damage

HDAC

HDAC1| HDAC2| HDAC3| HDAC6| HDAC8

Cancer

——

1316215-12-9

467.95

C24H26ClN5O3

>98% (HPLC)

Soluble in DMSO

ClC1=CC=CC=C1N(C2=CC=CC=C2)C3=NC=C(C=N3)C(NCCCCCCC(NO)=O)=O

2-((2-chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide

(-20℃)

With Ice Pack

≥ 2 years