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Devimistat (CPI-613) produces the selective toxicity against several tumor cell lines including H460 human lung cancer cells and Saos-2 human sarcoma cells with EC50 of 120 μM and 120 μM, respectively. CPI-613 (240 μM) also induces both apoptotic and non-apoptotic cell death in H460 human lung cancer and Saos-2 human sarcoma cells. Similarly, CPI-613 (10 mg/kg) also produces significant tumor growth inhibition of H460 human non-small cell lung carcinoma in mouse model.
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Source | Stem Cells Dev (2017). Figure 8. CPI-613 |
| Method | Amplex Ultra Red (AUR) assay | |
| Cell Lines | KGDHC and PDHC | |
| Concentrations | 10 μM | |
| Incubation Time | 15 min | |
| Results | At lower concentrations, KMV was not as effective as CPI-613 at suppressing ROS formed by pyruvate metabolism. This is in contrast to mitochondria oxidizing α- ketoglutarate where KMV and CPI-613 elicited similar effects. |
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Source | Stem Cells Dev (2017). Figure 5. CPI-613 |
| Method | Amplex Ultra Red (AUR) assay | |
| Cell Lines | KGDHC and PDHC | |
| Concentrations | 150 μM | |
| Incubation Time | 15 min | |
| Results | It had been previously shown that 150 μM CPI-613 is effective at inhibiting PDHC and KGDHC. It is important to emphasize that albumin needs to be excluded from reaction mixtures since it can interfere with the CPI-613 mediated inhibition of PDHC or KGDHC. |
| Cell Experiment | |
|---|---|
| Cell lines | BxPC-3 human pancreatic tumor cells |
| Preparation method | BxPC-3 human pancreatic tumor cells were treated with 50 µM CPI-613 or sham treated (i.e., vehicle), whereas the non-transformed NIH-3T3 mouse fibroblast cells were treated with 100 µM CPI-613 or sham treatment (i.e., vehicle), for 6 hours. The duration of treatment with CPI-613 was based on a time course experiment which measured the time taken to induce death in 10-15% of the cells. At the end of the 6-hour treatment period, live cells were selected based on Trypan blue exclusion and quantified using a hemocytometer. |
| Concentrations | 100 µM |
| Incubation time | 6 h |
| Animal Experiment | |
|---|---|
| Animal models | CD1-Nu/Nu female mice |
| Formulation | PBS |
| Dosages | 25 mg/kg |
| Administration | i.p. |
| Molecular Weight | 388.59 |
| Formula | C22H28O2S2 |
| CAS Number | 95809-78-2 |
| Solubility (25°C) | DMSO 48 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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