Inhibitors Targeting the F-BOX Proteins

Abstract

F-box proteins are involved in multiple cellular processes through ubiquitylation and consequent degradation of targeted substrates. Any significant mutation in F-box protein-mediated proteolysis can cause human malformations. The various cellular processes F-box proteins involved include cell proliferation, apoptosis, invasion, angiogenesis, and metastasis. To target F-box proteins and their associated signaling pathways for cancer treatment, researchers have developed thousands of F-box inhibitors. The most advanced inhibitor of FBW7, NVD-BK M120, is a powerful P13 kinase inhibitor that has been proven to bring about apoptosis in cancerous human lung cells by disrupting levels of the protein known as MCL1. Moreover, F-box Inhibitors have demonstrated their efficacy for treating certain cancers through targeting particular mutated proteins. This paper explores the key studies on how F-box proteins act and their contribution to malignancy development, which fabricates an in-depth perception of inhibitors targeting the F-box proteins and their signaling pathways that eventually isolate the most promising approach to anti-cancer treatments.

Keywords: E3 ligase; F-box protein; Ubiquitin; cancer progression; small molecule inhibitor; substrate.