160) As a preclinical step, effect of GS-343074 and GS-424044 were evaluated against ten canine cancer cell lines for antiproliferative effect. |
PMID:23672437 DOI:10.1111/vco.12038 |
2015 Veterinary and comparative oncology |
* Novel acyclic nucleotide analogues GS-343074 and GS-424044 demonstrate antiproliferative and pro-apoptotic activity in canine neoplastic cell lines. |
- 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. |
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(2)48 cells | (15)6 tissues | (28)3 patients, | (41)2 growth |
(3)33 and | (16)5 cells, | (29)3 research | (42)2 initiation |
(4)32 cell | (17)5 progression | (30)3 was | (43)2 prevention |
(5)23 patients | (18)5 registries | (31)2 (GC) | (44)2 registry |
(6)15 in | (19)4 at | (32)2 biology | (45)2 study |
(7)14 is | (20)4 deaths | (33)2 but | (46)2 susceptibility |
(8)12 risk | (21)4 has | (34)2 can | (47)2 than |
(9)12 screening | (22)4 mortality | (35)2 care | (48)2 treated |
(10)12 stem | (23)3 (CRC) | (36)2 development | (49)2 treatment |
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(13)6 are | (26)3 metabolism | (39)2 drugs |
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