Fluorinated Inhibitors of Cathepsin K
Cathepsin K (CTSK) is a lysosomal cysteine protease primarily expressed in osteoclasts. It plays a crucial role in bone tissue resorption by degrading components of the extracellular matrix (ECM), particularly type I collagen. This enzyme has become a promising therapeutic target for the treatment of osteoporosis, a disease characterized by decreased bone mineral density. Recently, CTSK has also been shown to be overexpressed in tumor cells, contributing to the development of various cancers, including breast and prostate cancer.
The first objective of this project is to rationally explore the impact of incorporating fluorine atoms into CTSK inhibitors to improve their biological profile. The second objective is to develop a PROTAC (proteolysis-targeting chimera) targeting CTSK to study its biology and its involvement in different diseases, as well as its potential use as a tool in cancer therapy.