CPI-613
(Synonyms: 6,8-双(苄硫基)辛酸,CPI-613) 目录号 : GC14921
An inhibitor of α-ketoglutarate dehydrogenase
Cas No.:95809-78-2
Sample solution is provided at 25 µL, 10mM.
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CPI-613 is a first-in-class anti-cancer agent [1].
CPI-613 is developed to target the pyruvate dehydrogenase complex which is a key mitochondrial enzyme of anaerobic glycolysis in tumor cells. The pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (KGDH) play critical roles in the interconversion of both pyruvate and alpha-ketoglutarate to key biosynthetic intermediates in mitochondrial carbon metabolism process. The complex of the two enzymes requires lipoate to be as a co-factor. CPI-613 is a derivative of lipoate and therefore inhibits the energy metabolism in mitochondria [1].
CPI-613 inhibited growth of various acute myeloid leukemia (AML) cell lines with IC50 values of 16.4, 13.4 and 12.2 μM in HL60, Jurkat and K562 cells, respectively. The treatment of CPI-613 induced apoptosis dose-dependently in OCI-AML3 and K562 cells. In H460 cells cultured in medium containing glutamine and pyruvate as the predominant carbon sources, treatment of CPI-613initiallyreversible ATP level reduction. When the treatment time was above 2 hours, cells became irreversibly committed to death. In the JC-1 localization assay, CPI-613 reduced mitochondrial membrane potential significantly. Besides that, when combined with doxorubicin, the treatment showed synergistic effects in Jurkat and K562 cells [1 and 2].
CPI-613 was proved to have little side-effect toxicity in expected therapeutic dose ranges and be well tolerated at very high doses (the maximum tolerated dose in mice was ca.100 mg/kg). Administration of CPI-613 at dose of 10 mg/kg resulted in significant inhibition of tumor growth in mice bearing H460 human non-small cell lung carcinoma. CPI-613 also caused robust tumor growth inhibition in mouse model of human pancreatic tumor (BxPC-3) xenografts [2].
References:
[1] Pardee T S, Levitan D, Hurd D. Altered mitochondrial metabolism as a target in acute myeloid leukemia. J ClinOncol, 2011, 29(suppl): 6590-6591.
[2] Zachar Z, Marecek J, Maturo C, et al. Non-redox-active lipoatederivates disrupt cancer cell mitochondrial metabolism and are potent anticancer agents in vivo. Journal of molecular medicine, 2011, 89(11): 1137-1148.
| Cell experiment [1]: | |
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Cell lines |
NCI-H460 NSCLC human tumor cells |
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Preparation method |
The solubility of this compound in DMSO is >19.5mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
50-300 μM |
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Applications |
In series of tumor cell lines, CPI-613 efficiently killed tumor cells. In H460 human lung cancer cells cultured in medium containing pyruvate and glutamine, CPI-613 significantly reduced ATP levels within less than 60 min and this reduction was initially reversible. After longer treatment times, cells become irreversibly to execute cell death. CPI-613 differentially inhibited PDH activity in normal and tumor cells. |
| Animal experiment [1]: | |
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Animal models |
nude mouse human tumor xenograft model of a pancreatic tumor cell (BxPC-3) and a non-small cell lung tumor cell (H460) |
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Dosage form |
25 mg/kg; once weekly; four treatments at 7-day intervals; intraperitoneal injection.10 mg/kg; once weekly, three times weekly, or five times weekly; intraperitoneal injection. |
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Application |
In human pancreatic (BxPC-3) xenograft carrying nude mouse, CPI-613 significantly inhibited tumor growth and over 40% of treated animals survived until the experiment was terminated at over 8 months (259 days). CPI-613 (10 mg/kg) also inhibited the growth of H460 human non-small cell lung carcinoma and the maximum tolerated dose was ca.100 mg/kg. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Zachar Z, Marecek J, Maturo C, et al. Non-redox-active lipoatederivates disrupt cancer cell mitochondrial metabolism and are potent anticancer agents in vivo. Journal of molecular medicine, 2011, 89(11): 1137-1148. |
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| Cas No. | 95809-78-2 | SDF | |
| 别名 | 6,8-双(苄硫基)辛酸,CPI-613 | ||
| 化学名 | 6,8-bis(benzylsulfanyl)octanoic acid | ||
| Canonical SMILES | C1=CC=C(C=C1)CSCCC(CCCCC(=O)O)SCC2=CC=CC=C2 | ||
| 分子式 | C22H28O2S2 | 分子量 | 388.59 |
| 溶解度 | ≥ 19.45 mg/mL in DMSO, ≥ 93.2 mg/mL in EtOH | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5734 mL | 12.867 mL | 25.7341 mL |
| 5 mM | 0.5147 mL | 2.5734 mL | 5.1468 mL |
| 10 mM | 0.2573 mL | 1.2867 mL | 2.5734 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet