Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a successful PROTAC. Some PROTACs with a triazole linker have displayed promising anticancer activity. This review provides an overview of PROTACs with a triazole scaffold and discusses its structure–activity relationship. Important milestones in the development of PROTACs are addressed and a critical analysis of this drug discovery strategy is also presented.

No abstract

No abstract

: In recent decades, much attention has been given to cyclopropyl scaffolds, which commonly exist in natural products and synthetic organic molecules. Clinical drug molecules with cyclopropyl rings are an area of focus in therapeutic research due to its interesting chemical properties and unique pharmacology activity. These molecular drugs against different targets are applicable in some therapeutic treatment fields including cancer, infection, respiratory disorder, cardiovascular and cerebrovascular diseases, dysphrenia, nervous system disorders, endocrine and metabolic disorders, skin disease, digestive disorders, urogenital diseases, otolaryngological and dental diseases, and eye diseases. This review is a guide for pharmacologists who are in search of valid preclinical/clinical drug compounds where the progress, from 1961 to the present day, of approved marketed drugs containing cyclopropyl scaffold is examined.