Molecular Weight(MW): 388.59
CPI-613, a lipoate analog, inhibits mitochondrial enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase in NCI-H460 cell line, disrupts tumor cell mitochondrial metabolism. Phase 2.
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Choose Selective Dehydrogenase Inhibitors
|Description||CPI-613, a lipoate analog, inhibits mitochondrial enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase in NCI-H460 cell line, disrupts tumor cell mitochondrial metabolism. Phase 2.|
In vitro, 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 disrupts H460 cancer cell mitochondrial metabolism including inhibition of PDH complex activity and loss of mitochondrial membrane potential in a time- and drug dose-dependent fashion. In addition, CPI-613 (240 μM) also induces both apoptotic and non-apoptotic cell death in H460 human lung cancer and Saos-2 human sarcoma cells. 
|In vivo||CPI-613 (25 mg/kg) has potent anticancer activity in a human tumor xenograft model of of a pancreatic tumor cell (BxPC-3). Similarly, CPI-613 (10 mg/kg) also produces significant tumor growth inhibition of H460 human non-small cell lung carcinoma in mouse model. Besides, CPI-613 produces little or no side-effect toxicity in expected therapeutic dose ranges in large animal models and has the maximum tolerated dose of 100 mg/kg in mice. |
|In vitro||DMSO||78 mg/mL (200.72 mM)|
|Ethanol||78 mg/mL (200.72 mM)|
|In vivo||1% DMSO+30% polyethylene glycol+1% Tween 80||30 mg/mL|
* 1 mg/ml means slightly soluble or insoluble.
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01520805||Withdrawn||Acute Myeloid Leukemia (AML)|Myelodysplastic Syndrome (MDS)||Cornerstone Pharmaceuticals, Inc.||January 2016||Phase 2|
|NCT01830322||Withdrawn||Metastatic Pancreatic Adenocarcinoma||Cornerstone Pharmaceuticals, Inc.||January 2014||Phase 2|
|NCT01832857||Terminated||Cancer||Cornerstone Pharmaceuticals, Inc.||June 2013||Phase 2|
|NCT01768897||Completed||Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities|Adult Acute Myeloid Leukemia With Del(5q)|Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)|Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)|Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)|Recurrent Adult Acute Myeloid Leukemia||Wake Forest University Health Sciences|National Cancer Institute (NCI)||January 2013||Phase 1|
|NCT01034475||Completed||Advanced Hematologic Malignancies||Wake Forest University Health Sciences||March 2010||Phase 1|
|NCT00907166||Suspended||Cancer|Pancreatic Cancer|Pancreatic Carcinoma||Cornerstone Pharmaceuticals, Inc.||May 2009||Phase 1|Phase 2|
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