Citarinostat (ACY241) 是第二代有效的,口服活性,高选择性的HDAC6抑制剂,IC50为 2.6 nM (HDAC1,HDAC2,HDAC3 和 HDAC8 的 IC50分别为 35 nM,45 nM,46 nM 和 137 nM)。Citarinostat 具有抗癌作用。
生物活性 | Citarinostat (ACY241) is a second generation potent, orally active and high-selectiveHDAC6inhibitor with anIC50of 2.6 nM (IC50s of 35 nM, 45 nM, 46 nM and 137 nM forHDAC1,HDAC2,HDAC3andHDAC8, respectively). Citarinostat has anticancer effects[1]. |
IC50& Target[1] | HDAC6 2.6 nM (IC50) | HDAC1 35 nM (IC50) | HDAC2 45 nM (IC50) | HDAC3 46 nM (IC50) | HDAC8 137 nM (IC50) | HDAC7 7300 nM (IC50) |
|
体外研究 (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[1]. The single agent viability IC50of 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[1].
Western Blot Analysis[1] 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. |
|
体内研究 (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[1].
Animal Model: | Female athymic nude mice (7-week-old) injected with TOV-21G cells[1] | 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. |
|
Clinical Trial | |
分子量 | |
性状 | |
Formula | |
CAS 号 | |
运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
|
溶解性数据 | In Vitro: DMSO : ≥ 30 mg/mL(64.11 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 2.1370 mL | 10.6849 mL | 21.3698 mL | 5 mM | 0.4274 mL | 2.1370 mL | 4.2740 mL | 10 mM | 0.2137 mL | 1.0685 mL | 2.1370 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (5.34 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.34 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (5.34 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.34 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (5.34 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.34 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
|