MedKoo product information:

 Gemcitabine elaidate

Description of Gemcitabine elaidate: Gemcitabine elaidate (also known as CO-101; CP-4126) is a lipophilic, unsaturated fatty acid ester derivative of gemcitabine (dFdC), an antimetabolite deoxynucleoside analogue, with potential antineoplastic activity. Upon hydrolysis intracellularly by esterases, the prodrug gemcitabine is converted into the active metabolites difluorodeoxycytidine di- and tri-phosphate (dFdCDP and dFdCTP) by deoxycytidine kinase. dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and apoptosis. Due to its lipophilicity, gemcitabine 5'-elaidic acid ester exhibits an increased cellular uptake and accumulation, resulting in an increased conversion to active metabolites, compared to gemcitabine. In addition, this formulation of gemcitabine may be less susceptible to deamination and deactivation by deoxycytidine deaminase. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

CO-101 is currently being developed by Clovis, who licensed its first oncology product candidate, CO-101 (formerly CP-4126), currently in development for the treatment of pancreatic cancer. CO-101 was discovered by, and licensed from, Clavis Pharma ASA, a clinical stage oncology focused pharmaceutical company based in Oslo, Norway.

Current developer:    Clovis Oncology (licensee), Clavis Pharma ASA (originator).

CO-101 is a new, patented, cytotoxic drug which consists of gemcitabine, an anticancer nucleoside analog, coupled to a fatty acid chain. CO-101 was designed to improve upon the efficacy of gemcitabine by enabling the drug to enter cancer cells without requiring uptake by a specific transporter molecule. Intravenous CO-101 is currently being evaluated in a clinical trial in advanced pancreatic cancer. Gemcitabine is the current standard treatment for advanced pancreatic cancer, and is also used in combination with other chemotherapy agents for the treatment of other cancers, including ovarian, non-small cell lung, and breast cancer. As a hydrophilic molecule, the entry of gemcitabine into tumor cells is dependent upon the expression of specific membrane transporter proteins, particularly hENT1. (source: http://www.clovisoncology.com/products/prod_co101.php).

1: Adema AD, Smid K, Losekoot N, Honeywell RJ, Verheul HM, Myhren F, Sandvold ML, Peters GJ. Metabolism and accumulation of the lipophilic deoxynucleoside analogs elacytarabine and CP-4126. Invest New Drugs. 2011 Oct 15. [Epub ahead of print] PubMed PMID: 22002019.

2: Adema AD, Losekoot N, Smid K, Kathmann I, Myhren F, Sandvold ML, Peters GJ. Induction of resistance to the lipophilic cytarabine prodrug elacytarabine (CP-4055) in CEM leukemic cells. Nucleosides Nucleotides Nucleic Acids. 2010 Jun;29(4-6):394-9. PubMed PMID: 20544525.

3: Sandvold ML, Galmarini C, Myhren F, Peters G. The activity of the lipophilic nucleoside derivatives elacytarabine and CP-4126 in a panel of tumor cell lines resistant to nucleoside analogues. Nucleosides Nucleotides Nucleic Acids. 2010 Jun;29(4-6):386-93. PubMed PMID: 20544524.

4: Bergman AM, Adema AD, Balzarini J, Bruheim S, Fichtner I, Noordhuis P, Fodstad O, Myhren F, Sandvold ML, Hendriks HR, Peters GJ. Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models. Invest New Drugs. 2011 Jun;29(3):456-66. Epub 2010 Jan 12. PubMed PMID: 20066470; PubMed Central PMCID: PMC3076580.

5: Adema AD, Laan AC, Myhren F, Fichtner I, Verheul HM, Sandvold ML, Peters GJ. Cell cycle effects of fatty acid derivatives of cytarabine, CP-4055, and of gemcitabine, CP-4126, as basis for the interaction with oxaliplatin and docetaxel. Int J Oncol. 2010 Jan;36(1):285-94. PubMed PMID: 19956857.

6: Galmarini CM, Myhren F, Sandvold ML. CP-4055 and CP-4126 are active in ara-C and gemcitabine-resistant lymphoma cell lines. Br J Haematol. 2009 Jan;144(2):273-5. Epub 2008 Nov 19. PubMed PMID: 19036103.