title: Preclinical efficacy of thioxanthone SR271425 against transplanted solid tumors of mouse and human origin.
abstract: A highly active and broadly active thioxanthone has been identified: N-[[1-[[2-(Diethylamino)ethyl]amino]-7-methoxy-9-oxo-9H-thioxanthen++ +-4-yl] methylformamide (SR271425, BCN326862, WIN71425). In preclinical testing against a variety of subcutaneously growing solid tumors, the following %T/C and Log10 tumor cell kill (LK) values were obtained: Panc-03 T/C = 0, 5/5 cures; Colon-38 (adv. stage) T/C = 0, 3/5 cures, 4.9 LK; Mam-16/C T/C = 0, 3.5 LK; Mam-17/0 T/C = 0, 2.8 LK; Colon-26 T/C = 0, 1/5 cures, 3.2 LK; Colon-51 T/C = 0, 2.7 LK; Panc-02 T/C = 0, 3.1 LK; B16 Melanoma T/C = 13%, 4.0 LK; Squamous Lung-LC12 (adv. stage) T/C = 14%, 4.9 LK; BG-1 human ovarian T/C = 16%, 1.3 LK; WSU-Brl human breast T/C = 25%, 0.8 LK. The agent was modestly active against doxorubicin (Adr)-resistant solid tumors: Mam-17/AdrT/C =23%, 0.8 LK; and Mam-16/C/Adr T/C = 25%, 1.0 LK, but retained substantial activity against a taxol-resistant tumor: Mam-16/C/taxol T/C = 3%, 2.4 LK. SR271425 was highly active against IV implanted leukemias, L1210 6.3 LK and AML1498 5.3 LK. The agent was equally active both by the IV and oral routes of administration, although requiring approximately 30% higher dose by the oral route. Based on its preclinical antitumor profile, it may be appropriate to evaluate SR271425 in clinical trials.
authors.affiliation: Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Corbett
authors.forename: C
authors.initials: C
authors.lastname: Panchapor
authors.forename: L
authors.initials: L
authors.lastname: Polin
authors.forename: N
authors.initials: N
authors.lastname: Lowichik
authors.forename: S
authors.initials: S
authors.lastname: Pugh
authors.forename: K
authors.initials: K
authors.lastname: White
authors.forename: J
authors.initials: J
authors.lastname: Kushner
authors.forename: J
authors.initials: J
authors.lastname: Meyer
authors.forename: J
authors.initials: J
authors.lastname: Czarnecki
authors.forename: S
authors.initials: S
authors.lastname: Chinnukroh
authors.forename: M
authors.initials: M
authors.lastname: Edelstein
authors.forename: P
authors.initials: P
authors.lastname: LoRusso
authors.forename: L
authors.initials: L
authors.lastname: Heilbrun
authors.forename: J P
authors.initials: JP
authors.lastname: Horwitz
authors.forename: C
authors.initials: C
authors.lastname: Grieshaber
authors.forename: R
authors.initials: R
authors.lastname: Perni
authors.forename: M
authors.initials: M
authors.lastname: Wentland
authors.forename: S
authors.initials: S
authors.lastname: Coughlin
authors.forename: S
authors.initials: S
authors.lastname: Elenbaas
authors.forename: R
authors.initials: R
authors.lastname: Philion
authors.forename: J
authors.initials: J
authors.lastname: Rake
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000627:therapeutic use; D013892:Thioxanthenes / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D013892:Thioxanthenes; C402303:SR 271425; D004317:Doxorubicin; D017239:Paclitaxel