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Vet Comp Oncol. 2015 Sep;13(3):246-54. doi: 10.1111/vco.12038. Epub 2013 May 15.

Novel acyclic nucleotide analogues GS-343074 and GS-424044 demonstrate antiproliferative and pro-apoptotic activity in canine neoplastic cell lines.

Author information

1
School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
2
Animal Cancer Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
3
Department of Research and Development, Gilead Sciences Inc, Foster City, CA, USA.
4
Paul P Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.

Abstract

GS-9219, a novel prodrug of the nucleotide analogue 9-(2-phosphonylmethoxyethyl) guanine (PMEG) has significant activity as monotherapy in dogs with non-Hodgkin's lymphoma. Phase I trials have been initiated in humans based on the encouraging activity observed in canine lymphoma. Two new analogues of GS-9219 (GS-343074 and GS-424044) were recently produced for evaluation as potential novel antineoplastic agents against solid tumours. As a preclinical step, effect of GS-343074 and GS-424044 were evaluated against ten canine cancer cell lines for antiproliferative effect. Both analogues displayed antiproliferative activity against multiple canine cancer cell lines, although GS-343074 was more potent and of broader spectrum compared to GS-424044. Flow cytometric analysis of cells that experienced growth inhibition support apoptotic death as a mechanism of action for both analogues. On the basis of in vitro results described here, GS-343074 and GS-424044 show promise as novel anticancer agents in canine cancer.

KEYWORDS:

chemotherapy; comparative oncology; in vitro models; oncology; small animal

PMID:
23672437
PMCID:
PMC3971014
DOI:
10.1111/vco.12038
[Indexed for MEDLINE]
Free PMC Article
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