95809-78-2CPI-613

产品属性：

Cas No.95809-78-2

别名

化学名 6,8-bis(benzylsulfanyl)octanoic acid

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  For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition     Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述：
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.