CCF642 是一种有效的蛋白质二硫键异构酶 (PDI) 抑制剂，IC50为 2.9 μM。CCF642 在多发性骨髓瘤细胞中引起急性内质网 (ER) 应激，并伴随凋亡诱导的钙释放。CCF642 具有广泛的抗多发性骨髓瘤活性。
| 生物活性 | CCF642 is a potentprotein disulfideisomerases(PDI)inhibitor with anIC50of 2.9 μM. CCF642 causes acute endoplasmic reticulum (ER) stress in multiple myeloma cells accompanied by apoptosis-inducing calcium release. CCF642 has broad anti-multiple myeloma activity[1]. |
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体外研究
(In Vitro) | CCF642 (3 μM; 0.5-6 hours) increases PERK dimerization by phosphorylation and IRE1-α oligomerization within 30 minutes in KMS-12-PE confirming accumulation of misfolded ER proteins[1].
CCF642, a bone marrow-sparing compound, exhibits a submicromolar IC50in 10 of 10 multiple myeloma cell lines (MM1.S, MM1.R, KMS-12-PE, KMS-12-BM, NCI-H929, U266, RPMI 8226, JJN-3, HRMM.09-luc, 5TGM1-luc)[1].
Western Blot Analysis[1] | Cell Line: | MM1.S cells | | Concentration: | 3 μM | | Incubation Time: | 0.5, 1, 2, 4, 6 hours | | Result: | Increased PERK dimerization by phosphorylation and IRE1-α oligomerization within 30 minutes in KMS-12-PE confirming accumulation of misfolded ER proteins. |
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体内研究
(In Vivo) | CCF642 (10 mg/kg; i.p.; three times a week; for 24 days) significantly prolongs life of 5TGM1-luc-bearing mice and suppresses 5TGM1-luc growth as determined by life imaging[1].
| Animal Model: | C57BL/KaLwRij mice of 6 to 8 weeks of age with 5TGM1-luc[1] | | Dosage: | 10 mg/kg | | Administration: | i.p.; three times a week; for 24 days | | Result: | Significantly prolonged life of 5TGM1-luc–bearing mice and suppressed 5TGM1-luc growth as determined by life imaging. |
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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 : ≥ 30 mg/mL(79.27 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.6424 mL | 13.2118 mL | 26.4236 mL | | 5 mM | 0.5285 mL | 2.6424 mL | 5.2847 mL | | 10 mM | 0.2642 mL | 1.3212 mL | 2.6424 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: 0.62 mg/mL (1.64 mM); Suspended solution; Need ultrasonic
此方案可获得 0.62 mg/mL (1.64 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 6.2 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。 *以上所有助溶剂都可在本网站选购。
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