On January 28, Xiaokun Li , Chief Scientist at Oujiang Laboratory, Senior Researcher Moosa Mohammadi, Distinguished Researcher Gaozhi Chen , and their team at Oujiang Laboratory, in collaboration with Researcher Chen Lingfeng from Hangzhou Medical College, published a review titled “FGF-based drug discovery: advances and challenges” in the top-tier review journal Nature Reviews Drug Discovery. This review systematically summarizes the progress in developing therapeutic drugs for FGF-related metabolic diseases and provides new insights and directions for the development of such drugs.
Fibroblast growth factor (FGF) plays a crucial regulatory role in human development, metabolism, and tissue homeostasis. Historically, however, FGF was primarily recognized for its potential in promoting wound healing. In recent years, systematic elucidation of FGF's metabolic regulatory functions has provided crucial theoretical foundations for developing FGF-based therapeutics for metabolic disorders. Protein reconstituted variants like FGF19 and FGF21 show promising prospects for approval in treating primary sclerosing cholangitis and metabolic syndrome-associated steatohepatitis (MASH), respectively. Thus, the application of FGF in metabolic diseases has emerged as a new frontier in drug development.
This review comprehensively details the classification, metabolic regulatory functions, structural characteristics, and downstream signaling properties of FGFs. It systematically introduces FGF family members with metabolic regulatory functions, recent research advances in their metabolic regulation, and the progress of drug development. The review also emphasizes the importance of the “threshold model” for developing FGF-based therapeutics for metabolic diseases, while identifying challenges and potential directions for future drug development.
