Advances in the discovery of DHPMs as Eg5 inhibitors for the management of breast cancer and glioblastoma: A review

Abstract

Breast cancer and gliobalstoma are the most aggressive types of diseases causing serious health issues. Potent anticancer molecules are facing serious side effects which arouse the need for newer molecules with significant clinical efficacy and safety. Eg5 protein is over-expressed in many cancer types making it the most consequential target of researchers. Past two decades dihydropyrimidinones (DHPM) scaffold-containing derivatives have shown promising pharmacological potential as Eg5 inhibitors. Monastrol is the first cell permeable prototype molecule of the DHPM class and acts as a specific Eg5 inhibitor that binds allosterically to the α2/loop5/helix α3 region in the Eg5 protein pocket, however, found to be a weak Eg5 inhibitor (IC50 = 30 µM). Nevertheless, many lead-optimized molecules are several fold more potent than monastrol but unfortunately, they do not gain clinical success. This review summarizes recent updates on DHPM derivatives as Eg5 inhibitors enlightening their therapeutic potential as anti-breast cancer and antitumor agents, especially from the period of 2018 to 2022.

Keywords

• Dihydropyrimidinones
• Eg5 inhibitors
• Breast cancer
• Glioblastoma