| 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
|
| リソース情報 |
| ヒト・動物細胞 |
Li-7(RCB1941) |
