Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 6; p. 614
• Main Authors: Dai, Shuyan, Zhou, Zhan, Chen, Zhuchu, Xu, Guangyu, Chen, Yongheng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18-06-2019; MDPI
• Subjects: Adenocarcinoma; Adenosine triphosphate; Binding sites; Cancer; Cell adhesion & migration; Cell membranes; Clinical trials; Fibroblast growth factor receptors; Fibroblast Growth Factors - metabolism; Fibroblast Growth Factors - physiology; Fibroblasts; Growth factor receptors; Growth factors; Hepatocellular carcinoma; Humans; kinase inhibitor; Kinases; Laboratories; Ligands; Lung cancer; Lung carcinoma; Metastases; Mutation; Ovarian cancer; Protein Kinase Inhibitors - chemistry; Proteins; Pyrazoles; Quinoxalines; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Fibroblast Growth Factor - antagonists & inhibitors; Receptors, Fibroblast Growth Factor - metabolism; Receptors, Fibroblast Growth Factor - physiology; Review; Signal Transduction - drug effects; structure; targeted therapy; Tumors; Tyrosine; Urothelial carcinoma; China; kinase inhibitor; targeted therapy; fibroblast growth factor receptors; structure
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8060614

Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases expressed on the cell membrane that play crucial roles in both developmental and adult cells. Dysregulation of FGFRs has been implicated in a wide variety of cancers, such as urothelial carcinoma, hepatocellular carcinoma, ovarian cancer and lung adenocarcinoma. Due to their functional importance, FGFRs have been considered as promising drug targets for the therapy of various cancers. Multiple small molecule inhibitors targeting this family of kinases have been developed, and some of them are in clinical trials. Furthermore, the pan-FGFR inhibitor erdafitinib (JNJ-42756493) has recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic or unresectable urothelial carcinoma (mUC). This review summarizes the structure of FGFR, especially its kinase domain, and the development of small molecule FGFR inhibitors.