New kinase and HDAC hybrid inhibitors: recent advances and perspectives

Abstract

Cancer is the second most common cause of death worldwide. It can easily acquire resistance to treatments, demanding new therapeutic strategies, such as simultaneous inhibition of kinase and HDAC enzymes with hybrid inhibitors. Different approaches to this have varied according to their targets, with a few common trends, such as the usage of heterocycle scaffolds for kinase interaction, especially pyrimidine and quinazolines, and hydroxamic acids and benzamides for HDAC inhibition. Besides the hybrid compounds developed focusing on the inhibition tyrosine kinase and receptor tyrosine kinase, many advances have occurred in the development of serine-threonine kinase/HDAC and lipid kinase/HDAC novel compounds. Here, the latest strategies employed in this research area will be reviewed, alongside trends in inhibitor design, and observed gaps will be punctuated.