論文 - 詳細
| RRC ID | 65071 |
|---|---|
| 著者 | Perera TPS, Jovcheva E, Mevellec L, Vialard J, De Lange D, Verhulst T, Paulussen C, Van De Ven K, King P, Freyne E, Rees DC, Squires M, Saxty G, Page M, Murray CW, Gilissen R, Ward G, Thompson NT, Newell DR, Cheng N, Xie L, Yang J, Platero SJ, Karkera JD, Moy C, Angibaud P, Laquerre S, Lorenzi MV. |
| タイトル | Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor. |
| ジャーナル | Mol Cancer Ther |
| Abstract |
Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor (FGFR) family members are associated with increased tumor growth, metastasis, angiogenesis, and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases. JNJ-42756493 shows rapid uptake into the lysosomal compartment of cells in culture, which is associated with prolonged inhibition of FGFR signaling, possibly due to sustained release of the inhibitor. In xenografts from human tumor cell lines or patient-derived tumor tissue with activating FGFR alterations, JNJ-42756493 administration results in potent and dose-dependent antitumor activity accompanied by pharmacodynamic modulation of phospho-FGFR and phospho-ERK in tumors. The results of the current study provide a strong rationale for the clinical investigation of JNJ-42756493 in patients with tumors harboring FGFR pathway alterations. Mol Cancer Ther; 16(6); 1010-20. ©2017 AACR. |
| 巻・号 | 16(6) |
| ページ | 1010-1020 |
| 公開日 | 2017-6-1 |
| DOI | 10.1158/1535-7163.MCT-16-0589 |
| PII | 1535-7163.MCT-16-0589 |
| PMID | 28341788 |
| MeSH | Animals Antineoplastic Agents / administration & dosage Antineoplastic Agents / pharmacokinetics Antineoplastic Agents / pharmacology* Cell Line, Tumor Cell Proliferation / drug effects Disease Models, Animal Dose-Response Relationship, Drug Drug Discovery* Humans Lysosomes / metabolism Male Mice Molecular Targeted Therapy Phosphorylation Protein Binding Protein Kinase Inhibitors / administration & dosage Protein Kinase Inhibitors / pharmacokinetics Protein Kinase Inhibitors / pharmacology* Pyrazoles / administration & dosage Pyrazoles / pharmacokinetics Pyrazoles / pharmacology* Quinoxalines / administration & dosage Quinoxalines / pharmacokinetics Quinoxalines / pharmacology* Receptors, Fibroblast Growth Factor / antagonists & inhibitors* Signal Transduction / 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 | 4 |
| 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 | Ba/F3 |