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. 1995 Aug;86(8):776-82.
doi: 10.1111/j.1349-7006.1995.tb02468.x.

A new water-soluble camptothecin derivative, DX-8951f, exhibits potent antitumor activity against human tumors in vitro and in vivo

I Mitsui  1 , E Kumazawa, Y Hirota, M Aonuma, M Sugimori, S Ohsuki, K Uoto, A Ejima, H Terasawa, K Sato
Affiliations

A new water-soluble camptothecin derivative, DX-8951f, exhibits potent antitumor activity against human tumors in vitro and in vivo

I Mitsui et al. Jpn J Cancer Res. 1995 Aug.

Abstract

CPT-11, a semisynthetic derivative of camptothecin, exhibited strong antitumor activity against lymphoma, lung cancer, colorectal cancer, gastric cancer, ovarian cancer, and cervical cancer. CPT-11 is a pro-drug that is converted to an active metabolite, SN-38, in vivo by enzymes such as carboxylesterase. We synthesized a water-soluble and non-pro-drug analog of camptothecin, DX-8951f. It showed both high in vitro potency against a series of 32 malignant cell lines and significant topoisomerase I inhibition. The anti-proliferative activity of DX-8951f, as indicated by the mean GI50 value, was about 6 and 28 times greater than that of SN-38 or SK&F 10486-A (Topotecan), respectively. These three derivatives of camptothecin showed similar patterns of differential response among 32 cell lines, that is, their spectra of in vitro cytotoxicity were almost the same. The antitumor activity of three doses of DX-8951f administered i.v. at 4-day intervals against human gastric adenocarcinoma SC-6 xenografts was greater than that of CPT-11 or SK&F 10486-A. Moreover, it overcame P-glycoprotein-mediated multi-drug resistance. These data suggest that DX-8951f has a high antitumor activity and is a potential therapeutic agent.

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References

    1. ) Wall , M. E. , Wani , M. C. , Cook , C. E. , Palmar , K. H. , McPhail , A. T. and Sim , G. A.Plant antitumor agents, I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptothecaacuminata . J. Am. Chem. Soc. , 88 , 3888 – 3890 ( 1966. ).
    1. ) Hsiang , Y.‐H. , Hertzberg , R. , Hecht , S. and Liu , L. F.Camptothecin induces protein‐linked DNA breaks via mammalian DNA topoisomerase I . J. Biol Chem. , 260 , 14873 – 14878 ( 1985. ). - PubMed
    1. ) Hsiang , Y.‐H. and Liu , L. F.Identification of mammalian DNA topoisomerase I as an intracellular target of the anticancer drug camptothecin . Cancer Res. , 48 , 1722 – 1726 ( 1988. ). - PubMed
    1. ) Hertzberg , R. P. , Caranfa , M. J. and Hecht , S. M.On the mechanism of topoisomerase I inhibition by camptothecin: evidence for binding to an enzyme‐DNA complex . Biochemistry , 28 , 4629 – 4638 ( 1989. ). - PubMed
    1. ) Gallo , R. C. , Whang‐Peng , J. and Adamson , R. H.Studies on the antitumor activity, mechanism of action, and cell cycle effects of camptothecin . J. Natl. Cancer Inst. , 46 , 789 – 795 ( 1971. ). - PubMed

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