CB-5083 是一种首创的,有效的,具有口服活性的,选择性p97 AAA ATPase/VCP抑制剂。CB-5083 抑制 p97 AAA ATP 酶结构域 D2,IC50为 11 nM。
生物活性 | CB-5083 is a first-in-class, potent, selective, and orally bioavailable inhibitor of thep97AAA ATPase/VCP. CB-5083 selectively inhibitsp97through its D2 site with theIC50of 11 nM[1]。 |
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体外研究 (In Vitro) | CB-5083 shows cell killing potency with IC50s of 0.68, 0.68, 1.03, and 0.49 μM for lung carcinoma A549 CTG, A549 K48, A549 CHOP, and A549 p62, respectively[1].
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体内研究 (In Vivo) | CB-5083 (75 mg/kg; oral administration; qd; for 2 weeks) shows antitumor activity in an HCT 116 tumor xenograft model[1]. CB-5083 exhibits terminal elimination half-life (T1/2=2.56 h), moderate oral bioavailability (mouse 41%) and Cmax(mouse 7.95 μM) following oral administration (25 mg/kg) in female nude mice[1]. CB-5083 exhibits terminal elimination half-life (T1/2=2.83 h) due to high plasma clearance (5.9 mL/min/kg respectively) combined with large volumes of distribution (418 mL/kg respectively) following intravenous administration (3.0 mg/kg) in female nude mice[1]. CB-5083 has good metabolic stability with a 102 min T1/2in a mouse liver microsomal stability study and a 172 min T1/2in a hepatocyte stability study[1].
Animal Model: | Nu/Nu nude female mice bearing established human tumor xenografts derived from HCT 116 colon[1] | Dosage: | 75 mg/kg | Administration: | Administered orally using every day (qd) dosing, for 2 weeks. | Result: | Showed more profound antitumor activity. |
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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(241.86 mM;Need ultrasonic) 配制储备液 1 mM | 2.4186 mL | 12.0928 mL | 24.1856 mL | 5 mM | 0.4837 mL | 2.4186 mL | 4.8371 mL | 10 mM | 0.2419 mL | 1.2093 mL | 2.4186 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: 50%PEG300 50% saline Solubility: 10 mg/mL (24.19 mM); Clear solution; Need ultrasonic 2. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (6.05 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.05 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。 3. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (6.05 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.05 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。 4. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (6.05 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.05 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。
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