Homocamptothecins: E-ring modified CPT analogues.

O Lavergne; D Demarquay; P G Kasprzyk; D C Bigg

doi:10.1111/j.1749-6632.2000.tb07029.x

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Homocamptothecins: E-ring modified CPT analogues.

O Lavergne·D Demarquay·P G Kasprzyk·D C Bigg

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Abstract

Homocamptothecins (hCPT) are modified camptothecins (CPT) with a seven-membered beta-hydroxylactone instead of the naturally occurring six-membered alpha-hydroxylactone. This E-ring modification fully conserves the ability to stabilize topo I-DNA single-strand breaks and stimulates high levels of DNA cleavage. A key feature is the irreversibility of E-ring opening, which should give reduced toxicity. Substituted hCPTs have been selected for their high antiproliferative activity on a panel of tumor cell lines, including those with cross resistance, and were found to be active at very low doses in a variety of human tumor xenografts when administered orally. BN 80915, a difluoro-hCPT, has entered clinical trials.

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Animals Antineoplastic Agents Camptothecin Enzyme Inhibitors Humans Xenograft Model Antitumor Assays Journal Article Review

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O Lavergne, D Demarquay, P G Kasprzyk, D C Bigg. 2000. Homocamptothecins: E-ring modified CPT analogues.. https://doi.org/10.1111/j.1749-6632.2000.tb07029.x

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