Recent advances in CDC7 kinase inhibitors: Novel strategies for the treatment of cancers and neurodegenerative diseases

Abstract

Cell division cycle 7 (CDC7) plays an indispensable regulatory role in various cellular processes, encompassing the initiation of DNA replication and the maintenance of replication checkpoints. However, dysregulation of CDC7 protein levels is closely associated with the development and progression of several human diseases, particularly cancers and neurodegenerative diseases. Therefore, targeting the CDC7 kinase is deemed a potential avenue for disease management. Currently, a few CDC7 inhibitors have progressed to clinical trials. Nevertheless, limited clinical efficacy coupled with severe adverse reactions necessitates the implementation of innovative technologies to enhance therapeutic effectiveness and minimize adverse events. Herein, we highlight the structure, biological functions and significance in disease progression of CDC7, and discuss the preclinical and clinical states of CDC7 inhibitors. Our focus centers on the structure-activity relationship (SAR) and binding modes of CDC7 inhibitors, offering perspectives on novel CDC7-targeting drugs for clinical application.