Abstract | PURPOSE: METHODS: Previously, we introduced the quinoxaline derivative GK13 as a lead compound for TGase 2 inhibitor. The inhibitory effect of GK13 on TGase 2 was improved in GK921 (3-(phenylethynyl)-2-(2-(pyridin-2-yl)ethoxy)pyrido[3,2-b] pyrazine). GK921 efficacy was tested using sulforhodamine in vitro as well as a xenograft tumor models using ACHN and CAKI-1 RCC cells. RESULTS:
GK921 showed cytotoxicity to RCC (average GI50 in eight RCC cell lines: 0.905 μM). A single treatment with GK921 almost completely reduced tumor growth by stabilizing p53 in the ACHN and CAKI-1 preclinical xenograft tumor models. CONCLUSION: TGase 2 inhibitor GK921 abrogates RCC growth in xenograft tumor models, suggesting the possibility of a new therapeutic approach to RCC.
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Authors | Bo Mi Ku, Se-Jin Kim, Nayeon Kim, Dongwan Hong, Yong-Bock Choi, Seon-Hyeong Lee, Young-Dae Gong, Soo-Youl Kim |
Journal | Journal of cancer research and clinical oncology
(J Cancer Res Clin Oncol)
Vol. 140
Issue 5
Pg. 757-67
(May 2014)
ISSN: 1432-1335 [Electronic] Germany |
PMID | 24610445
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3-(phenylethynyl)-2-(2-(pyridin-2-yl)ethoxy)pyrido(3,2-b)pyrazine
- Pyrazines
- Protein Glutamine gamma Glutamyltransferase 2
- Transglutaminases
- GTP-Binding Proteins
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Topics |
- Animals
- Carcinoma, Renal Cell
(drug therapy, genetics, pathology)
- Cell Line, Tumor
- Cell Proliferation
- GTP-Binding Proteins
(antagonists & inhibitors, biosynthesis)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Mice
- Protein Glutamine gamma Glutamyltransferase 2
- Pyrazines
(administration & dosage, pharmacology)
- Transglutaminases
(antagonists & inhibitors, biosynthesis)
- Xenograft Model Antitumor Assays
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