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

• Published in: Journal of medicinal chemistry Vol. 48; no. 7; pp. 2258 - 2261
• Main Authors: 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: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.04.2005; Amer Chemical Soc
• Subjects: 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; Chemistry, Medicinal; 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; Life Sciences & Biomedicine; Medical sciences; Mice; Microsomes, Liver - metabolism; Miscellaneous; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Topoisomerase I Inhibitors; Transplantation, Heterologous; GLYCOSIDES; DNA CLEAVAGE; COMPOUND 6-N-FORMYLAMINO-12,13-DIHYDRO-1,11-DIHYDROXY-13-(BETA-D-GLUCOPYRANOSYL)-5H-INDO NB-506; STAUROSPORINE; ANTICANCER AGENTS; TOPOISOMERASE-I; AGLYCONE; CYTOTOXICITY; BISINDOLYLMALEIMIDES; REBECCAMYCIN; Antineoplastic agent; Human; Carcinoma; Enzyme; DNA topoisomerase; Rodentia; Enzyme inhibitor; Cytotoxicity; Biological activity; Imide; Irinotecan; Vertebrata; Isomerases; Mammalia; Cell line; Mouse; Animal; Tumor; Glycoside; Fluorine Organic compounds; Chemical synthesis; Tumor cell
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm049090z

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.