CPI-1612 是一种高效的具有口服活性的EP300/CBP组蛋白乙酰转移酶 (HAT) 抑制剂,对于EP300 HAT的IC50值为 8.1 nM。CPI-1612 具有抗癌活性。
生物活性 | CPI-1612 is a highly potent, orally activeEP300/CBPhistone acetyltransferase(HAT)inhibitor with anIC50of 8.1 nM forEP300 HAT. CPI-1612 has an anticancer activity[1]. |
IC50& Target | IC50: 8.1 nM (EP300 HAT)[1] |
体外研究 (In Vitro) | CPI-1612 inhibits full length EP300 and full length CBP with IC50values<0.5 nM and 2.9 nM, respectively[1]. CPI-1612 inhibits H3K18Ac MSD (H3K18 = histone 3 lysine 18, MSD = meso scale discovery) and JEKO-1 cell proliferation with with IC50values 14 nM and<7.9 nM, respectively[1]. CPI-1612 (compound 17) shows weak activity in a hERG binding assay (IC50= 10.4 μM) and displayed moderate inhibition of CYP2C8 (IC50= 1.9 μM) and CYP2C19 (IC50= 2.7 μM)[1].
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体内研究 (In Vivo) | CPI-1612 (compound 17; 0.5 mg/kg; oral administration; twice a day; for 4 weeks) treatment shows 67% tumor growth inhibition (TGI) with concomitant reduction of H3K27Ac in plasma and reduction of H3K18Ac in the tumor[1]. While the oral exposure of CPI-1612 (compound 17) in dogs (0.5 mg/kg IV; 1.0 mg/kg PO; clearance = 0.42 L/h/kg, Vss= 3.7 L/kg, T1/2= 5.5 h, F% = 71; AUC/dose = 1691 h·mg/mL) and mice (1 mg/kg IV; 5 mg/kg PO; clearance = 3.8 L/h/kg, Vss= 2.0 L/kg, T1/2= 0.98 h, F% = 79; AUC/dose = 211 h·mg/mL) is good, the exposure in rats is limited by poor bioavailability (1.0 mg/kg IV; 5.0 mg/kg PO; clearance = 2.6 L/h/kg, Vss= 1.8 L/kg, T1/2= 1.2 h, F% = 9; AUC/dose = 35.6 h·mg/mL)[1]. A single dose of CPI-1612 is administered orally to CD-1 mice and brain and plasma exposures of CPI-1612 are measured at 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 h. CPI-1612 is highly brain-penetrant, showing a brain-to-plasma ratio of 0.35 after a single oral dose[1].
Animal Model: | C57B6 mice injected with JEKO-1 cells[1] | Dosage: | 0.5 mg/kg | Administration: | Oral administration; twice a day; for 4 weeks | Result: | Showed 67% tumor growth inhibition (TGI) at a dose of 0.5 mg/kg. |
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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 |
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溶解性数据 | In Vitro: DMSO : 100 mg/mL(221.96 mM;Need ultrasonic) 配制储备液 1 mM | 2.2196 mL | 11.0980 mL | 22.1961 mL | 5 mM | 0.4439 mL | 2.2196 mL | 4.4392 mL | 10 mM | 0.2220 mL | 1.1098 mL | 2.2196 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: 5 mg/mL (11.10 mM); Suspended solution; Need ultrasonic
此方案可获得 5 mg/mL (11.10 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例,取 100 μL 50.0 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%corn oil Solubility: ≥ 5 mg/mL (11.10 mM); Clear solution
此方案可获得 ≥ 5 mg/mL (11.10 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 50.0 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。
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