Discovery of a Fluoroindolo[2,3-a]carbazole Clinical Candidate with Broad Spectrum Antitumor Activity in Preclinical Tumor Models Superior to the Marketed Oncology Drug, CPT-11

Discovery of a Fluoroindolo[2,3-a]carbazole Clinical Candidate with Broad Spectrum Antitumor Activity in Preclinical Tumor Models Superior to the Marketed Oncology Drug, CPT-11

A series of fluoroglycosylated fluoroindolocarbazoles was examined with respect to their topoisomerase I activity, cytotoxicity, and selectivity. The lead clinical candidate from this series, BMS-250749, displays broad spectrum antitumor activity superior to CPT-11 against some preclinical xenograft...

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Veröffentlicht in:Journal of medicinal chemistry 2005-04, Vol.48 (7), p.2258-2261
Hauptverfasser: Saulnier, Mark G, Balasubramanian, Balu N, Long, Byron H, Frennesson, David B, Ruediger, Edward, Zimmermann, Kurt, Eummer, Jeffrey T, St. Laurent, Denis R, Stoffan, Karen M, Naidu, B. Narasimhulu, Mahler, Mikael, Beaulieu, Francis, Bachand, Carol, Lee, Frank Y, Fairchild, Craig R, Stadnick, Linda K, Rose, William C, Solomon, Carola, Wong, Henry, Martel, Alain, Wright, John J, Kramer, Robert, Langley, David R, Vyas, Dolatrai M
Format: Artikel
Sprache:eng
Schlagworte:
Animals
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Camptothecin - analogs & derivatives
Camptothecin - pharmacology
Carbazoles - chemical synthesis
Carbazoles - chemistry
Carbazoles - pharmacology
Cell Line, Tumor
Drug Evaluation, Preclinical
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
General aspects
Glucosides - chemical synthesis
Glucosides - chemistry
Glucosides - pharmacology
Humans
In Vitro Techniques
Indoles - chemical synthesis
Indoles - chemistry
Indoles - pharmacology
Medical sciences
Mice
Microsomes, Liver - metabolism
Miscellaneous
Pharmacology. Drug treatments
Topoisomerase I Inhibitors
Transplantation, Heterologous
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Zusammenfassung:A series of fluoroglycosylated fluoroindolocarbazoles was examined with respect to their topoisomerase I activity, cytotoxicity, and selectivity. The lead clinical candidate from this series, BMS-250749, displays broad spectrum antitumor activity superior to CPT-11 against some preclinical xenograft models, including curative antitumor activity against Lewis lung carcinoma.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm049090z