title: 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.
abstract: 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.
authors.affiliation: The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA. Mark.Saulnier@bms.com
authors.forename: Mark G
authors.initials: MG
authors.lastname: Saulnier
authors.forename: Balu N
authors.initials: BN
authors.lastname: Balasubramanian
authors.forename: Byron H
authors.initials: BH
authors.lastname: Long
authors.forename: David B
authors.initials: DB
authors.lastname: Frennesson
authors.forename: Edward
authors.initials: E
authors.lastname: Ruediger
authors.forename: Kurt
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Eummer
authors.forename: Denis R
authors.initials: DR
authors.lastname: St Laurent
authors.forename: Karen M
authors.initials: KM
authors.lastname: Stoffan
authors.forename: B Narasimhulu
authors.initials: BN
authors.lastname: Naidu
authors.forename: Mikael
authors.initials: M
authors.lastname: Mahler
authors.forename: Francis
authors.initials: F
authors.lastname: Beaulieu
authors.forename: Carol
authors.initials: C
authors.lastname: Bachand
authors.forename: Frank Y
authors.initials: FY
authors.lastname: Lee
authors.forename: Craig R
authors.initials: CR
authors.lastname: Fairchild
authors.forename: Linda K
authors.initials: LK
authors.lastname: Stadnick
authors.forename: William C
authors.initials: WC
authors.lastname: Rose
authors.forename: Carola
authors.initials: C
authors.lastname: Solomon
authors.forename: Henry
authors.initials: H
authors.lastname: Wong
authors.forename: Alain
authors.initials: A
authors.lastname: Martel
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Robert
authors.initials: R
authors.lastname: Kramer
authors.forename: David R
authors.initials: DR
authors.lastname: Langley
authors.forename: Dolatrai M
authors.initials: DM
authors.lastname: Vyas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077146:Irinotecan; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D059004:Topoisomerase I Inhibitors; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C500156:BMS 250749; D002227:Carbazoles; D005960:Glucosides; D007211:Indoles; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; D002166:Camptothecin