지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.1
- 수록면
- 326 - 331 (6page)
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We recently reported that Val-SN-38, a novel valine ester prodrug of SN-38, had greatly improved the intracellular accumulation of SN-38 in MCF-7 cell line, probably through enhanced uptake via amino acid transporters. In the present study, the efficacy of Val-SN-38 was further investigated both in vitro and in vivo. It was found that the in vitro cytotoxic effect of Val-SN-38 was similar to that of SN-38. Moreover, Val-SN-38 exhibited an equal potency to that of SN-38 in survival experiments in vivo. Because these results seemed to be contrary to the previous finding, further investigation was performed to find out the underlying cause of the contradiction. As only the lactone form is known to have cytotoxic activity, the proportion of lactone in Val-SN-38 and SN-38 was determined, but no differences were found. However, it turned out that Val-SN-38 had poor stability compared with SN-38, which resulted in a decrease in beneficial efficacy for Val-SN-38. Overall, the present study showed that a valine-added prodrug approach could be advantageous provided that the stability of the compound can be ensured. We believe this is a noteworthy study that unravels the discrepancy between intracellular accumulation and efficacy of valine-added prodrug.
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참고문헌 (24)
참고문헌 신청
Adane, E. D. / 2010 / Factors affecting the in vivo lactone stability and systemic clearance of the lipophilic camptothecin analogue AR-67 / Pharm. Res 27:1416~1425
Araki, E. / 1993 / Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11 / Jpn. J. Cancer Res 84:697~702
Balimane, P. V. / 1998 / Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir / Biochem. Biophys. Res. Commun 250:246~251
Burke, T. G. / 1993 / Preferential binding of the carboxylate form of camptothecin by human serum albumin / Anal. Biochem 212:285~287
Chu, X. Y. / 1997 / Multispecifi c organic anion transporter is responsible for the biliary excretion of the camptothecin derivative irinotecan and its metabolites in rats / J. Pharmacol. Exp. Ther 281:304~314
Araki, E. / 1993 / Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11 / Jpn. J. Cancer Res 84:697~702
Balimane, P. V. / 1998 / Direct evidence for peptide transporter (PepT1)-mediated uptake of a nonpeptide prodrug, valacyclovir / Biochem. Biophys. Res. Commun 250:246~251
Burke, T. G. / 1993 / Preferential binding of the carboxylate form of camptothecin by human serum albumin / Anal. Biochem 212:285~287
Chu, X. Y. / 1997 / Multispecifi c organic anion transporter is responsible for the biliary excretion of the camptothecin derivative irinotecan and its metabolites in rats / J. Pharmacol. Exp. Ther 281:304~314
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