論文 - 詳細
| RRC ID | 65145 |
|---|---|
| 著者 | Futami T, Okada H, Kihara R, Kawase T, Nakayama A, Suzuki T, Kameda M, Shindoh N, Terasaka T, Hirano M, Kuromitsu S. |
| タイトル | ASP5878, a Novel Inhibitor of FGFR1, 2, 3, and 4, Inhibits the Growth of FGF19-Expressing Hepatocellular Carcinoma. |
| ジャーナル | Mol Cancer Ther |
| Abstract |
Hepatocellular carcinoma is an aggressive cancer with poor prognosis. Fibroblast growth factor 19, a member of the fibroblast growth factor family, is a ligand for fibroblast growth factor receptor 4. Moreover, it plays a crucial role in the progression of hepatocellular carcinoma. ASP5878 is a novel inhibitor of fibroblast growth factor receptors 1, 2, 3, and 4 that is under development. It inhibits fibroblast growth factor receptor 4 kinase activity with an IC50 of 3.5 nmol/L. ASP5878 potently suppressed the growth of the fibroblast growth factor 19-expressing hepatocellular carcinoma cell lines Hep3B2.1-7, HuH-7, and JHH-7. In the Hep3B2.1-7 cell line, ASP5878 inhibited the phosphorylation of fibroblast growth factor receptor 4 and its downstream signaling molecules as well as induced apoptosis. Oral administration of ASP5878 at 3 mg/kg induced sustained tumor regression in a subcutaneous xenograft mouse model using Hep3B2.1-7. In HuH-7, an orthotopic xenograft mouse model, ASP5878 induced complete tumor regression and dramatically extended the survival of the mice. These results suggest that ASP5878 is a potentially effective therapeutic agent for hepatocellular carcinoma patients with tumors expressing fibroblast growth factor 19. Mol Cancer Ther; 16(1); 68-75. ©2016 AACR. |
| 巻・号 | 16(1) |
| ページ | 68-75 |
| 公開日 | 2017-1-1 |
| DOI | 10.1158/1535-7163.MCT-16-0188 |
| PII | 1535-7163.MCT-16-0188 |
| PMID | 27837028 |
| MeSH | Animals Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Apoptosis / drug effects Carcinoma, Hepatocellular / drug therapy Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / metabolism Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cell Proliferation / drug effects Disease Models, Animal Fibroblast Growth Factors / genetics* Gene Expression* Humans Liver Neoplasms / drug therapy Liver Neoplasms / genetics* Liver Neoplasms / metabolism Liver Neoplasms / pathology Male Mice Protein Kinase Inhibitors / chemistry Protein Kinase Inhibitors / pharmacology Pyrazoles / chemistry Pyrazoles / pharmacology* Pyrimidines / chemistry Pyrimidines / pharmacology* Receptors, Fibroblast Growth Factor / antagonists & inhibitors* Signal Transduction / drug effects Tumor Burden / drug effects Xenograft Model Antitumor Assays |
| IF | 5.615 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Li-7(RCB1941) |