Artificial agonists for receptor tyrosine kinases (RTKs): Design, classification, and therapeutic potential

: Receptor tyrosine kinases (RTKs), as core regulatory elements in cell signal transduction, play a critical role in maintaining physiological homeostasis. Imbalances in their activity are closely associated with tumorigenesis, metabolic disorders, and neurodegenerative diseases. Despite significant advancements in the development of RTK inhibitors over the past four decades, the therapeutic potential of strategies targeting RTK activation remains underexplored in regenerative medicine, metabolic disorders, and immune dysregulation. Physiological activation of RTKs is essential for tissue repair and the maintenance of metabolic homeostasis. Artificially designed RTK agonists can precisely modulate receptor activity by mimicking natural ligands or employing innovative molecular engineering approaches, offering a novel avenue for disease treatment. This review systematically examines the design, classification, and therapeutic potential of artificial RTK agonists, elucidating their unique mechanisms of action from four types of agents acting as agonists: peptides, DNA, small molecule compounds, and antibodies. Furthermore, it provides a theoretical foundation and practical guidance with clinical translational potential for the development of next-generation, highly efficient RTK agonists.