Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor

Perera, Timothy P.S., Jovcheva, Eleonora, Mevellec, Laurence, Vialard, Jorge, De Lange, Desiree, Verhulst, Tinne, Paulussen, Caroline, Van De Ven, Kelly, King, Peter, Freyne, Eddy, Rees, David C., Squires, Matthew, Saxty, Gordon, Page, Martin, Murray, Christopher W., Gilissen, Ron, Ward, George, Thompson, Neil T., Newell, Herbie, Cheng, Na, Xie, Liang, Yang, Jennifer, Platero, Suso J., Karkera, Jayaprakash D., Moy, Christopher, Angibaud, Patrick, Laquerre, Sylvie and Lorenzi, Matthew V. (2017) Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor. Molecular Cancer Therapeutics, 16 (6). pp. 1010-1020. ISSN 1535-7163

Full text not available from this repository.

Search Google Scholar

Abstract

©2017 American Association for Cancer Research. 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.

Item Type: Article
Subjects: Sciences
Divisions: Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > FHSW Executive
Depositing User: Michelle Marshall
Date Deposited: 21 Aug 2019 15:23
Last Modified: 18 Dec 2019 16:08
URI: http://sure.sunderland.ac.uk/id/eprint/11053

Actions (login required)

View Item View Item