Abstract
The design, synthesis, and biological characterization of an orally active prodrug (3) of gemcitabine are described. Additionally, the identification of a novel co-crystal solid form of the compound is presented. Valproate amide 3 is orally bioavailable and releases gemcitabine into the systemic circulation after passing through the intestinal mucosa. The compound has entered clinical trials and is being evaluated as a potential new anticancer agent.
MeSH terms
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Administration, Oral
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Transformation, Neoplastic
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Colonic Neoplasms / drug therapy
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Crystallization
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Crystallography, X-Ray
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Cytidine / chemistry
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Deoxycytidine / administration & dosage
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / chemistry
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Deoxycytidine / pharmacology
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Gemcitabine
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Humans
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Mice
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Models, Molecular
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Molecular Conformation
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Prodrugs / administration & dosage
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Prodrugs / chemical synthesis
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Prodrugs / chemistry*
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Prodrugs / pharmacology*
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Solubility
Substances
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Antineoplastic Agents
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Prodrugs
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Deoxycytidine
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Cytidine
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Gemcitabine