Delanzomib (CEP-18770) 是一种强效的具有口服活性的蛋白酶体的胰凝乳蛋白酶样活性 (chymotrypsin-like activity of the proteasome) 抑制剂，IC50为 3.8 nM。Delanzomib 抑制NF-κB活性，诱导癌细胞凋亡 (apoptotic)，并具有很强的抗血管生成和抗癌活性。
| 生物活性 | Delanzomib (CEP-18770) is a potent and orally activechymotrypsin-like activity of theproteasomeinhibitor with anIC50of 3.8 nM. Delanzomib inhibitsNF-κBactivity, inducescancercellapoptotic, and has strong antiangiogenic and anti-cancer activities[1]. |
| IC50& Target | IC50: 3.8 nM (Chymotrypsin-like activity of the proteasome)[1] |
体外研究
(In Vitro) | Delanzomib (CEP-18770; 20 nM; 12-24 hours) treatment results in a progressive appearance of cleaved caspases-3, -7, and -9 between 12 and 24 hours’exposure in the human MM cell lines, RPMI-8226, and U266[1].
Delanzomib (CEP-18770; 5-40 nM; 4-24 hours) treatment induces an accumulation of ubiquitinated proteins over 4 to 8 hours[1].
Delanzomib (CEP-18770) inhibits endothelial cell survival, vasculogenesis, and osteoclastogenesis in vitro; and displays a favorable cytotoxicity profile toward normal cells[1].
Apoptosis Analysis[1] | Cell Line: | RPMI-8226, U266, and K562 cells | | Concentration: | 20 nM | | Incubation Time: | 12 hours, 24 hours | | Result: | Resulted in a progressive appearance of cleaved caspases-3, -7, and -9 between 12 and 24 hours’exposure in the human MM cell lines. |
Western Blot Analysis[1] | Cell Line: | RPMI-8226, U266, and K562 cells | | Concentration: | 5 nM, 10 nM, 20 nM, 40 nM | | Incubation Time: | 4 hours, 8 hours, 12 hours, 24 hours | | Result: | Induced an accumulation of ubiquitinated proteins over 4 to 8 hours. |
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体内研究
(In Vivo) | Delanzomib (CEP-18770; 7.8-13 mg/kg; oral administration; twice a week; for 4 weeks) treatment results in a more sustained pharmacodynamic inhibition of proteasome activity in tumors relative to normal tissues, complete tumor regression of multiple myeloma (MM) xenografts and improves overall median survival in a systemic model of human MM[1].
| Animal Model: | SCID mice injected with RPMI 8226 cells[1] | | Dosage: | 7.8 mg/kg, 10 mg/kg, 13 mg/kg | | Administration: | Oral administration; twice a week; for 4 weeks | | Result: | Resulted in a more sustained pharmacodynamic inhibition of proteasome activity in tumors relative to normal tissues. |
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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(241.97 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.4197 mL | 12.0983 mL | 24.1967 mL | | 5 mM | 0.4839 mL | 2.4197 mL | 4.8393 mL | | 10 mM | 0.2420 mL | 1.2098 mL | 2.4197 mL |
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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: ≥ 2.17 mg/mL (5.25 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (5.25 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 21.7 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: 2.17 mg/mL (5.25 mM); Suspended solution; Need ultrasonic
此方案可获得 2.17 mg/mL (5.25 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 21.7 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: ≥ 2.17 mg/mL (5.25 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (5.25 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 21.7 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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