Pharmacological profiling of novel non-COX-inhibiting indole-pyran analogues of etodolac reveals high solid tumour activity of SDX-308 in vitro
2007 (English)In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 25, no 4, 297-303 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2007. Vol. 25, no 4, 297-303 p.
Antineoplastic Agents/*pharmacology, Cell Line; Tumor, Drug Screening Assays; Antitumor, Etodolac/*analogs & derivatives/*pharmacology, Female, Heterocyclic Compounds; 3-Ring/*pharmacology, Humans
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-15630DOI: 10.1007/s10637-007-9049-4ISI: 000247275600002PubMedID: 17440681OAI: oai:DiVA.org:uu-15630DiVA: diva2:43401