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Pharmacological pro...
Pharmacological profiling of novel non-COX-inhibiting indole-pyran analogues of etodolac reveals high solid tumour activity of SDX-308 in vitro
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- Lindhagen, Elin (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Cancer Pharmacology and Informatics
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- Rickardson, Linda (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Cancer Pharmacology and Informatics
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Elliott, Gary (author)
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Leoni, Lorenzo (author)
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- Nygren, Peter (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Cancer Pharmacology and Informatics
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- Larsson, Rolf (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Cancer Pharmacolcogy and Informatics
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- Åleskog, Anna (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper
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(creator_code:org_t)
- 2007-04-18
- 2007
- English.
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In: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 25:4, s. 297-303
- Related links:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- Antineoplastic Agents/*pharmacology
- Cell Line; Tumor
- Drug Screening Assays; Antitumor
- Etodolac/*analogs & derivatives/*pharmacology
- Female
- Heterocyclic Compounds; 3-Ring/*pharmacology
- Humans
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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