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Oslo, Norway

Peters G.J.,VU University Amsterdam | Adema A.D.,VU University Amsterdam | Bijnsdorp I.V.,VU University Amsterdam | Sandvold M.L.,Clavis Pharma
Nucleosides, Nucleotides and Nucleic Acids | Year: 2011

Many drugs that are currently used for the treatment of cancer have limitations, such as induction of resistance and/or poor biological half-life, which reduce their clinical efficacy. To overcome these limitations, several strategies have been explored. Chemical modification by the attachment of lipophilic moieties to (deoxy)nucleoside analogs should enhance the plasma half-life, change the biodistribution, and improve cellular uptake of the drug. Attachment of a lipophilic moiety to a phosphorylated (deoxy)nucleoside analog will improve the activity of the drugs by circumventing the rate-limiting activation step of (deoxy)nucleoside analogs. Encapsulating drugs in nanoparticles or liposomes protects the drug against enzymatic breakdown in the plasma and makes it possible to get lipophilic compounds to the tumor site. In this review, we discuss the considerable progress that has been made in increasing the efficacy of classic (deoxy)nucleoside and fluoropyrimidine compounds by chemical modifications and alternative delivery systems. Copyright © Taylor and Francis Group, LLC. Source


This invention provides methods and compositions for treating or otherwise ameliorating cancer in a subject, along with methods and compositions for measuring the levels of nucleoside transporters in a tumor and correlating this level to a predicated efficacy of a given anti-cancer drug regime, and methods and compositions for treating patients with low levels of hENT1 expression in cancer cells using a lipophilic gemcitabine analog such as gemcitabine-5-elaidate.


Patent
Clavis Pharma | Date: 2010-11-15

The present invention relates to parenteral formulations for certain long chain saturated and monounsaturated fatty acid derivatives of 2,2-difluorodeoxycytidine (Gemcitabine). In particular, the present invention relates to a parenteral pharmaceutical composition and a method of the preparation thereof, in order to accommodate therapeutically effective doses of the said derivatives ameliorating compliance in treatment of cancer.


Patent
Clavis Pharma | Date: 2011-07-01

The present invention relates to parenteral formulations for certain long chain saturated and monounsaturated fatty acid derivatives of 1--D-arabinofuranosylcytosine (cytarabine). In particular, the present invention relates to a parenteral pharmaceutical composition and a method of the preparation thereof, in order to accommodate therapeutically effective doses of the said derivatives ameliorating compliance in treatment of cancer.


Sandvold M.L.,Clavis Pharma | Galmarini C.,French National Center for Scientific Research | Myhren F.,Clavis Pharma | Peters G.,VU University Amsterdam
Nucleosides, Nucleotides and Nucleic Acids | Year: 2010

The clinical activity of pyrimidine analogues (araC and gemcitabine) is impaired by different mechanisms of resistance and several efforts to overcome this problem have been undertaken. Elacytarabine (CP-4055, araC-5'elaidic acid ester) and CP-4126 (gemcitabine-5'elaidic acid ester) are lipophilic fatty acid derivatives of the nucleoside analogues araC and gemcitabine, respectively, that are currently investigated in clinical trials in solid tumors and hematological malignancies. Here, we present results on the activity of elacytarabine and CP-4126 in a panel of tumor cell lines that are resistant to araC and gemcitabine and we discuss the potential use of these agents in the treatment of patients with drug resistance phenotypes. We conclude that elacytarabine and CP-4126 are active in cells with deficient nucleoside membrane transport and altered mismatch repair. These results should be taking into consideration for future clinical development of elacyatrabine and CP-4126. Copyright © 2010 Taylor and Francis Group, LLC. Source

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