Abstract
Ubiquitination, the structured degradation and turnover of cellular proteins, is regulated by the ubiquitin–proteasome system (UPS). Most proteins that are critical for cellular regulations and functions are targets of the process. Ubiquitination is comprised of a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types. Recent evidence indicates that targeting the UPS is effective for certain cancer treatment, but many more potential targets might have been previously overlooked. In this review, we will discuss the current state of small molecules that target various elements of ubiquitination. Special attention will be given to novel inhibitors of E3 ubiquitin ligases, especially those in the SCF family.
Acknowledgements
The authors thank the OpenEye Scientific Software and ChemAxon for their free academic licenses. The authors also thank the high-performance computing resources from Texas Advanced Computing Center.
Financial & competing interests disclosure
Shuxing Zhang is partially supported by CPRIT DP150086 and RP140244 as well as NSF CHE-1411859, NIH/NIGMS GM070737, and NIH/NCI P30CA016672. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.