Cathepsin-family cysteine protease (CTS)

Cathepsin-family cysteine proteases are a group of 11 human lysosomal enzymes (Cathepsins B, C, F, H, K, L, O, S, V, W, and X) that belong to the papain-like C1 peptidase family [1][2]. These enzymes are primarily responsible for terminal protein degradation within the endolysosomal system, but they also perform specialized functions such as prohormone processing, antigen presentation (Cathepsin S), and bone resorption (Cathepsin K) [2][3]. Under pathological conditions, these proteases are often overexpressed or secreted into the extracellular environment, where they degrade the extracellular matrix, facilitating tumor invasion, metastasis, and joint destruction in arthritis [4][5]. They also play a role in viral entry, as seen with SARS-CoV-2 and Ebola, where Cathepsin L/B cleave viral spike proteins to allow membrane fusion [6]. Therapeutic strategies focus on small-molecule inhibitors, though achieving selectivity among family members remains a significant challenge to avoid adverse effects like skin fibrosis or cardiovascular risks [7][8]. For instance, the development of the Cathepsin K inhibitor Odanacatib was discontinued due to an increased risk of stroke, highlighting the safety hurdles in this class [8]. Despite these challenges, they remain high-interest targets for conditions ranging from osteoporosis to COVID-19 and various solid tumors [4][6].

Other names

Cysteine cathepsinsLysosomal cysteine proteasesPapain-like cysteine proteasesC1 family peptidases

Small molecule inhibition of the catalytic cysteine residue within the enzyme active site, thereby blocking the hydrolysis of peptide bonds in target proteins [1][2].