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01-08-2007 | PRECLINICAL STUDIES

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

Authors: Elin Lindhagen, Linda Rickardson, Gary Elliott, Lorenzo Leoni, Peter Nygren, Rolf Larsson, Anna Åleskog

Published in: Investigational New Drugs | Issue 4/2007

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.

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Title: Pharmacological profiling of novel non-COX-inhibiting indole-pyran analogues of etodolac reveals high solid tumour activity of SDX-308 in vitro
Authors: Elin Lindhagen
Linda Rickardson
Gary Elliott
Lorenzo Leoni
Peter Nygren
Rolf Larsson
Anna Åleskog
Publication date: 01-08-2007
Publisher: Kluwer Academic Publishers-Plenum Publishers
Published in: Investigational New Drugs / Issue 4/2007
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-007-9049-4

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