Focal adhesion kinase inhibitors in fibrotic diseases therapy: Development and therapeutic potential

Abstract

Organ fibrosis, characterized by dysregulated extracellular matrix deposition due to abnormal tissue repair, remains a significant challenge in medical research. Although nintedanib and pirfenidone have been approved for pulmonary fibrosis, effective treatments for hepatic, cardiac, and renal fibrosis remain markedly limited. The focal adhesion kinase (FAK) has been extensively implicated in the pathogenesis of organ fibrosis, with FAK kinase inhibition emerging as a pivotal therapeutic strategy for fibrosis modulation. In this review, we present a comprehensive analysis of FAK's biological functions in fibrotic progression and review preclinical advancements in FAK inhibitor development. We focus on the classification of FAK inhibitors, emphasizing their binding patterns, pharmacodynamic efficacy, and selectivity profiles from the perspective of pharmaceutical chemists. Additionally, we propose strategic frameworks for development of novel drugs targeting FAK for the treatment of fibrosis. The findings discussed in this review can guide the development of FAK inhibitors for treating organ fibrosis and underscore potential challenges in the drug development process.