Title:Recent Developments in Medicinal Chemistry and Therapeutic
Potential of Anti-Cancer PROTACs-Based Molecules
Volume: 30
Issue: 14
关键词:
靶向蛋白质降解，PROTACs，泛素化，降解，结构活性关系，药物化学
摘要:
Background: PROTACs is an emerging technique that addresses the disease
causing proteins by targeting protein degradation. PROTACs molecules are bifunctional
small molecules that simultaneously bind to the protein of interest (POIs) and an E3 ligase
followed by ubiquitination and degradation of the protein of interest by the proteasome.
Objective: PROTACs technology offers many advantages over classical inhibition such as
PROTACs molecules can target intracellular proteins regardless of their function and have
good tissue distribution. They are capable to target mutated and overexpressed proteins,
thus potent molecules with the high degradation selectivity can be designed. Moreover,
PROTACs molecules can target the undruggable proteome which makes up almost 85%
of human proteins. Several PROTACs-based compounds have exhibited high therapeutic
potency and some of them are currently under clinical trials.
Methods: Current article gives a comprehensive overview of the current development of
PROTACs-based anticancer compounds along with the structure-activity relationship of
the reported molecules.
Results: The development of PROTACs-based compounds and related research regarding
medicinal chemistry is one of the most active and hot topics for research.
Conclusion: It is believed that the current review article can be helpful to understand the
logical design of more efficacious PROTACs-based molecules with less toxicity and more
selectivity.
