Abstract |
We developed an oral administration-compatible, small molecular weight antitumor agent, YM-201627 by screening for the inhibition of the proliferation of VEGF-stimulated HUVECs. YM-201627 selectively inhibited the proliferation of various endothelial cell lines induced by VEGF, bFGF, and FBS (at IC50s of 0.0039-0.12 microM), that would not be expected to have any direct antiproliferative effect on other cell types. YM-201627 inhibited angiogenesis in vitro at a concentration of 0.01 microM. In the in vivo studies, it inhibited microvessel formation induced by human melanoma A375 cells suspended in Matrigel (86% with twice-daily doses of 30 mg/kg). Moreover, once-daily oral dosing of YM-201627 to mice bearing A375 xenografts elicited significant antitumor activity (73% with daily doses of 10 mg/kg). These results suggest that YM-201627 is a selective growth inhibitor of endothelial cells, which may be useful for treatment of solid tumors.
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Authors | Nobuaki Amino, Yukitaka Ideyama, Mayumi Yamano, Sadao Kuromitsu, Katsunori Tajinda, Kiyohiro Samizu, Akira Matsuhisa, Masafumi Kudoh, Masayuki Shibasaki |
Journal | Cancer letters
(Cancer Lett)
Vol. 238
Issue 1
Pg. 119-27
(Jul 08 2006)
ISSN: 0304-3835 [Print] Ireland |
PMID | 16095812
(Publication Type: Journal Article)
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Chemical References |
- Angiogenesis Inducing Agents
- Antineoplastic Agents
- Imidazoles
- YM-201627
- Vascular Endothelial Growth Factor Receptor-2
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Topics |
- Administration, Oral
- Angiogenesis Inducing Agents
(pharmacology)
- Animals
- Antineoplastic Agents
(therapeutic use)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Drug Screening Assays, Antitumor
- Endothelial Cells
(drug effects)
- Humans
- Imidazoles
(chemistry, therapeutic use)
- Melanoma, Experimental
(drug therapy)
- Mice
- Mice, Inbred Strains
- Phosphorylation
(drug effects)
- Vascular Endothelial Growth Factor Receptor-2
(analysis, drug effects)
- Xenograft Model Antitumor Assays
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