Investigational New Drugs

, Volume 25, Issue 4, pp 297–303

Pharmacological profiling of novel non-COX-inhibiting indole-pyran analogues of etodolac reveals high solid tumour activity of SDX-308 in vitro

  • Elin Lindhagen
  • Linda Rickardson
  • Gary Elliott
  • Lorenzo Leoni
  • Peter Nygren
  • Rolf Larsson
  • Anna Åleskog
PRECLINICAL STUDIES

DOI: 10.1007/s10637-007-9049-4

Cite this article as:
Lindhagen, E., Rickardson, L., Elliott, G. et al. Invest New Drugs (2007) 25: 297. doi:10.1007/s10637-007-9049-4

Summary

SDX-308 and SDX-309 are potent indole-pyran analogues of SDX-101 (R-etodolac) which has anti-tumour activity unrelated to cyclooxygenase-2 inhibition. Their cytotoxic activity was further studied herein using a well-characterized human tumour cell-line panel containing ten cell lines, as well as in 58 primary tumour cell samples from a variety of diagnoses. The indole-pyran analogues of SDX-101 were in general considerably more active in both cancer cell lines and primary tumour samples. Low cross-reactivity with standard agents was observed, indicating a unique mechanism of action. No apparent influence on efficacy was observed via classical mechanisms of multidrug-resistance. SDX-101 and SDX-309 showed higher relative activity in haematological compared to solid tumour samples, while SDX-308 had pronounced solid-tumour activity. High SDX-308 cytotoxic efficacy was observed in non-small cell lung cancer, renal cancer and ovarian cancer samples, and also in chronic lymphocytic leukaemia. In conclusion, the indole-pyran analogues showed a favourable pharmacological profile and represent a potentially important new class of drugs for cancer treatment.

Keywords

Anticancer drug Etodolac Indole-pyran SDX-101 SDX-308 SDX-309 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Elin Lindhagen
    • 1
  • Linda Rickardson
    • 1
  • Gary Elliott
    • 2
  • Lorenzo Leoni
    • 2
  • Peter Nygren
    • 1
  • Rolf Larsson
    • 1
  • Anna Åleskog
    • 3
  1. 1.Uppsala University HospitalUppsalaSweden
  2. 2.Salmedix Inc.San DiegoUSA
  3. 3.Division of HaematologyUppsala University HospitalUppsalaSweden