Bcl-2: research progress from target to launched drug / 药学学报

Apoptosis is an important self-stabilizing mechanism of multicellular organisms, which plays a vital role in the development of normal living organisms and the maintenance of tissue homeostasis. The abnormalities in apoptosis often lead to body lesions including tumors. Studies have shown that Bcl-2 protein with anti-apoptosis activity is an important target in the treatment of cancer. After nearly two decades of efforts, many small molecule Bcl-2 inhibitors have been discovered to induce cell apoptosis. The small-molecule Bcl-2 inhibitor, venetoclax, was developed based on fragment-based drug design strategy and approved by the FDA in 2016 for clinical application. This agent is the first approved small-molecule drug inhibiting Bcl-2 through protein-protein interaction to induce cell apoptosis. The achievement of venetoclax benefits from a combination of drug discovery technologies and represents a milestone in the history of drug discovery. In this review we will introduce the current progress in Bcl-2 inhibitors.

Histone deacetylase 6: structure, functions and development of selective inhibitors / 药学学报

Histone deacetylase 6 (HDAC6) is an unique subtype of histone deacetylases with two tandem deacetylase domains and substrate specificity for non-histone proteins. It is involved in many important physiological and pathological processes and has become a promising therapeutic target in recent decades. Different kinds of potent HDAC6-selective inhibitors have been reported around the world. This paper reviews the progress in the study of structure and functions of HDAC6 as well as the development of HDAC6-selective inhibitors.