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CPI-613

Description of CPI-613: CPI-613  is a racemic mixture of the enantiomers of a synthetic alpha-lipoic lipoic acid analogue with potential chemopreventive and antineoplastic activities. Although the exact mechanism of action is unknown, alpha-lipoic acid analogue CPI-613 has been shown to inhibit metabolic and regulatory processes required for cell growth in solid tumors. Both enantiomers in the racemic mixture exhibit antineoplastic activity. The mechanism-of-action of CPI-613 appears distinct from the current classes of anti-cancer agents used in the clinic. CPI-613 demonstrates both in vitro and in vivo anti-tumor activity. CPI-613 was known to strongly disrupt tumor mitochondrial metabolism. CPI-613 disruption of tumor mitochondrial metabolism is followed by efficient commitment to cell death by multiple, apparently redundant pathways, including apoptosis, in all tested cancer cell lines. Further, CPI-613 shows strong antitumor activity in vivo against human non-small cell lung and pancreatic cancers in xenograft models with low side-effect toxicity. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer: Cornerstone Pharmaceuticals.

CPI-613, currently developed by Cornerstone Pharmaceuticals,  is the lead candidate from a new chemical class that, through a novel mechanism of action, targets metabolic changes considered to be common to many, if not all, cancer types. CPI-613 is currently being evaluated in several ongoing Phase I/II trials. CPI-613 was granted orphan drug status by the US FDA for pancreatic cancer, which has a poor prognosis, spreads rapidly and often goes undetected in its early stages.

Accoring to  Cornerstone Pharmaceuticals's website, in November of 2009, CPI-613 was named one of the “top most interesting oncology projects available for partnering” by Windhover Information, a leading provider of healthcare industry analysis.  CPI-613's key features found in preclinical tests include (1) active across a broad spectrum of cancer types (solid tumor and hematologic); (2) induces cancer cell death in animal models of human cancers with no toxic effect on normal cells at therapeutic levels; (3) demonstrates 100% efficacy against every human cancer type tested in cell culture.

Highlight of recent study using CPI-613

Interim phase I trial results using CPI-613 for patients with relapsed and refractory hematologic malignancies (data published in Dec. 2011).  Accoring to Cornerstone Pharmaceuticals's news release -  To date, eleven patients have been treated with at least one cycle of CPI-613. Interim clinical data suggests that altered lipid and mitochondrial metabolism are viable targets in acute leukemias. CPI-613 is a novel agent that has activity against several acute leukemia cell lines in vitro and in vivo and demonstrates activity in patients with relapsed AML and Myelodysplastic Syndrome (MDS). Several patients experienced significant clinical benefit, including a sustained complete remission when treated with CPI-613 as a single agent. Only minor toxicities were observed.  (source: 53rd Annual American Society of Hematology Meeting)

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