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.
Saulnier MG, Balasubramanian BN, Long BH, Frennesson DB, Ruediger E, Zimmermann K, Eummer JT, St Laurent DR, Stoffan KM, Naidu BN, Mahler M, Beaulieu F, Bachand C, Lee FY, Fairchild CR, Stadnick LK, Rose WC, Solomon C, Wong H, Martel A, Wright JJ, Kramer R, Langley DR, Vyas DM.
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.