Octanoic acid, 6,8-bis[(phenylMethyl)thio]-

Description

CPI-613 (95809-78-2) is a lipoic acid analog which potently disrupts mitochondrial metabolism with selectivity for tumor cells in vitro and shows strong antitumor activity in vivo.1?? Inhibits alpha-ketoglutarate dehydrogenase (KGDH) by a redox mechanisms selectively in tumor cells.2 Inhibits pyruvate dehydrogenase (PDH) as a mechanistically distinct, non-redox, effect.1,2 A novel anticancer agent with a mitochondria-targeted mode of action with non-genotoxic properties.3. Has been used (along with PS48) to induce a Warburg-like metabolic state in fibroblasts.4 Combination treatment of CPI-613 and chloroquine inhibits the progression of clear cell sarcoma in a mouse model.5

Uses

CPI 613 is a class of non-redox-active lipoate derivative that disrupts cancer cell mitochondrial metabolism and are potent anticancer agents in vivo.

Uses

6,8-Bis(benzylthio)-octanoic acid has been used as pyruvate dehydrogenase (PDH) inhibitor:

• to study its effects on neurite outgrowth in primary mouse dorsal root ganglia cells
• to induce α-smooth muscle actin (αSMA) and pro-collagen I expression and to assess PDH enzyme activity in whole-cell lysates
• to validate basal respiration in tissue respirometry

Biochem/physiol Actions

6,8-Bis(benzylthio)-octanoic acid (CPI-613) is a lipoate analog. It acts as a mitochondrial disrupter by blocking the mitochondrial enzymes pyruvate dehydrogenase and α-ketoglutarate dehydrogenase.

storage

Store at +4°C

References

1) Zachar et al. (2011), Non-redox-active Lipoate Derivates Disrupt Cancer Cell Mitochondrial Metabolism and Are Potent Anticancer Agents in Vivo; J. Mol. Med. (Berl), 89 1137 2) Stuart et al. (2014), A Strategically designed Small Molecule Attacks Alpha-ketoglutarate Dehydrogenase in Tumor Cells Through a Redox Process; Cancer Metab., 2 4 3) Dorsam and Fahrer (2016), The Disulfide Compound α-lipoic Acid and Its Derivatives: A Novel Class of Anticancer Agents Targeting Mitochondria; Cancer Lett., 371(1) 12 4) Mordhorst et al. (2018), Pharmacologic Reprogramming Designed to Induce a Warburg Effect in Porcine Fetal Fibroblasts Alters Gene Expression and Quantities of Metabolites From Conditioned Media Without Increased Cell Proliferation; Cell Reprogram., 20 38 5) Egawa et al. (2018), Therapeutic Potential of CPI-613 for Targeting Tumorous Mitochondrial Energy Metabolism and Inhibiting Autophagy in Clear Cell Sarcoma; PLoS One, 13(6) e0198940