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Investigational New Drugs

, Volume 17, Issue 1, pp 17–27 | Cite as

Preclinical efficacy of thioxanthone SR271425 against transplanted solid tumors of mouse and human origin

  • Thomas H. Corbett
  • Chiab Panchapor
  • Lisa Polin
  • Nancy Lowichik
  • Susan Pugh
  • Kathryn White
  • Juiwanna Kushner
  • Jennifer Meyer
  • Jennifer Czarnecki
  • Salina Chinnukroh
  • Matthew Edelstein
  • Patricia LoRusso
  • Lance Heilbrun
  • Jerome P. Horwitz
  • Charles Grieshaber
  • Robert Perni
  • Mark Wentland
  • Susan Coughlin
  • Steven Elenbaas
  • Richard Philion
  • James Rake
Article

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-Br1 human breast T/C = 25%, 0.8 LK. The agent was modestly active against doxorubicin (Adr)-resistant solid tumors: Mam-17/Adr T/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.

Thioxanthone SR 271425 antitumor preclinical 

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Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Thomas H. Corbett
    • 1
  • Chiab Panchapor
    • 1
  • Lisa Polin
    • 1
  • Nancy Lowichik
    • 1
  • Susan Pugh
    • 1
  • Kathryn White
    • 1
  • Juiwanna Kushner
    • 1
  • Jennifer Meyer
    • 1
  • Jennifer Czarnecki
    • 1
  • Salina Chinnukroh
    • 1
  • Matthew Edelstein
    • 1
  • Patricia LoRusso
    • 1
  • Lance Heilbrun
    • 1
  • Jerome P. Horwitz
    • 1
  • Charles Grieshaber
    • 1
  • Robert Perni
    • 1
  • Mark Wentland
    • 2
  • Susan Coughlin
    • 3
  • Steven Elenbaas
    • 4
  • Richard Philion
    • 4
  • James Rake
    • 4
  1. 1.Karmanos Cancer Institute, Wayne State University School of MedicineDetroit
  2. 2.Department of ChemistryRensselaer Polytechnic InstituteTroy
  3. 3.Rhone PoulencCollegeville
  4. 4.Sanofi Research; a division of Sanofi Pharmaceuticals Inc.MalvernUSA

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