| http://purl.uniprot.org/citations/15687373 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15687373 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15687373 | http://www.w3.org/2000/01/rdf-schema#comment | "Capecitabine is an oral prodrug of 5-fluorouracil that is indicated for the treatment of breast and colorectal cancers. A three-step in vivo-targeted activation process requiring carboxylesterases, cytidine deaminase, and thymidine phosphorylase converts capecitabine to 5-fluorouracil. Carboxylesterases hydrolyze capecitabine's carbamate side chain to form 5'-deoxy-5-fluorocytidine (5'-DFCR). This study examines the steady-state kinetics of recombinant human carboxylesterase isozymes carboxylesterase (CES) 1A1, CES2, and CES3 for hydrolysis of capecitabine with a liquid chromatography/mass spectroscopy assay. Additionally, a spectrophotometric screening assay was utilized to identify drugs that may inhibit carboxylesterase activation of capecitabine. CES1A1 and CES2 hydrolyze capecitabine to a similar extent, with catalytic efficiencies of 14.7 and 12.9 min(-1) mM(-1), respectively. Little catalytic activity is detected for CES3 with capecitabine. Northern blot analysis indicates that relative expression in intestinal tissue is CES2 > CES1A1 > CES3. Hence, intestinal activation of capecitabine may contribute to its efficacy in colon cancer and toxic diarrhea associated with the agent. Loperamide is a strong inhibitor of CES2, with a K(i) of 1.5 muM, but it only weakly inhibits CES1A1 (IC(50) = 0.44 mM). Inhibition of CES2 in the gastrointestinal tract by loperamide may reduce local formation of 5'-DFCR. Both CES1A1 and CES2 are responsible for the activation of capecitabine, whereas CES3 plays little role in 5'-DFCR formation."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.org/dc/terms/identifier | "doi:10.1124/jpet.104.081265"xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.org/dc/terms/identifier | "doi:10.1124/jpet.104.081265"xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Sun Z."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Sun Z."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Bosron W.F."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Bosron W.F."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Hurley T.D."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Hurley T.D."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Murry D.J."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Murry D.J."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Davis W.I."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Davis W.I."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Sanghani S.P."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Sanghani S.P."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Quinney S.K."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/author | "Quinney S.K."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/name | "J. Pharmacol. Exp. Ther."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/name | "J. Pharmacol. Exp. Ther."xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/pages | "1011-1016"xsd:string |
| http://purl.uniprot.org/citations/15687373 | http://purl.uniprot.org/core/pages | "1011-1016"xsd:string |