{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:13:34Z","timestamp":1791274414300,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2006,7,1]],"date-time":"2006-07-01T00:00:00Z","timestamp":1151712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>This study aimed to investigate the gastrointestinal stability and the cellular uptake characteristics of l-valyl-ara-C, a peptidomimetic prodrug of ara-C (cytarabine). After the synthesis of l-valyl-ara-C via the incorporation of l-valine into the N4-amino group of the cytosine ring in ara-C, the gastrointestinal stability of l-valyl-ara-C was examined using artificial gastric juice and artificial intestinal fluids. The cellular uptake characteristics of l-valyl-ara-C were also examined in Caco-2 cells. The disappearance half-life of l-valyl-ara-C was 2.2 h in artificial gastric juice, while the degradation of l-valyl-ara-C was negligible in artificial intestinal fluid and also in the supernatant above the Caco-2 cell monolayer during the 2-h incubation. The cellular accumulation of l-valyl-ara-C was 5-fold higher than that of ara-C in Caco-2 cells. Furthermore, the cellular uptake of l-valyl-ara-C did not increase proportionally to the increase in drug concentration. The cellular accumulation of l-valyl-ara-C was significantly reduced in the presence of uridine, p-aminohippurate, tetraethylammonium and small dipeptides, while it was not changed in the presence of l-valine and benzoic acid, suggesting that l-valyl-ara-C could interact with multiple uptake transporters, including peptide transporters, organic anion and cation transporters and nucleoside transporters, but might not interact with amino acid transporters. In conclusion, l-valyl-ara-C could be effective to improve the oral absorption of ara-C via the carrier-mediated transport pathway.<\/jats:p>","DOI":"10.1211\/jpp.58.7.0007","type":"journal-article","created":{"date-parts":[[2006,6,17]],"date-time":"2006-06-17T17:51:22Z","timestamp":1150566682000},"page":"927-932","source":"Crossref","is-referenced-by-count":21,"title":["Enhanced cellular uptake of Ara-C via a peptidomimetic prodrug, L-valyl-ara-C in Caco-2 cells"],"prefix":"10.1093","volume":"58","author":[{"given":"Eun-Pa","family":"Cheon","sequence":"first","affiliation":[{"name":"College of Pharmacy, Chosun University , 375 Seosuk-dong, Gwangju,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Hee","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chosun University , 375 Seosuk-dong, Gwangju,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Kyung","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chosun University , 375 Seosuk-dong, Gwangju,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,7,1]]},"reference":[{"key":"2024103109342404900_cit1","doi-asserted-by":"crossref","first-page":"202","DOI":"10.2165\/00003088-198308030-00002","article-title":"Clinical pharmacokinetics of commonly used anticancer drugs","volume":"8","author":"Balis","year":"1983","journal-title":"Clin. 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