Abstract
Human cathepsin L belongs to the cathepsin family of proteolytic enzymes with primarily an endopeptidase activity. Although its primary functions were originally thought to be only of a housekeeping enzyme that degraded intracellular and endocytosed proteins in lysosome, numerous recent studies suggest that it plays many critical and specific roles in diverse cellular settings. Not surprisingly, the dysregulated function of cathepsin L has manifested itself in several human diseases, making it an attractive target for drug development. Unfortunately, several redundant and isoform-specific functions have recently emerged, adding complexities to the drug discovery process. To address this, a series of chemical biology tools have been developed that helped define cathepsin L biology with exquisite precision in specific cellular contexts. This review elaborates on the recently developed small molecule inhibitors and probes of human cathepsin L, outlining their mechanisms of action, and describing their potential utilities in dissecting unknown function.
Highlights
Lysosomes play critical roles in human biology receiving, trafficking, processing, and degrading biological molecules from seminal cellular processes, such as endocytosis, phagocytosis, autophagy and secretion
The focus of this review is on human cathepsin L, a ubiquitously expressed endopeptidase whose involvement in several human diseases has emerged in recent years
The developed compound certainly harbors the key traits of an effective activity-based probe, as the authors duly envisioned its significance in deciphering cathepsin L biology in the coming years
Summary
Lysosomes play critical roles in human biology receiving, trafficking, processing, and degrading biological molecules from seminal cellular processes, such as endocytosis, phagocytosis, autophagy and secretion. The focus of this review is on human cathepsin L, a ubiquitously expressed endopeptidase whose involvement in several human diseases has emerged in recent years These include liver fibrosis, Type I and II diabetes, cardiac and bone, immune and kidney disorders [12,13,14,15,16,17,18,19,20,21,22,23,24] In addition, its role in a wide variety of highly invasive forms of cancer is Molecules 2020, 25, 698; doi:10.3390/molecules25030698 www.mdpi.com/journal/molecules. Named so because of its abilities to inhibit cathepsin L (IC50 = 4.68 nM; Ki. 4.68 nM; Ki = 95 pM) activity, sialostatin L abrogates the protective proteolytic activity of host cells at.
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