Human and non-target proteases

Human and non-target proteases represent a vast collection of enzymes, collectively known as the degradome, which are responsible for the hydrolysis of peptide bonds (Rawlings et al., 2018, Nucleic Acids Res). This group includes over 500 human enzymes categorized into classes such as serine, cysteine, aspartic, threonine, and metalloproteases, each playing vital roles in processes like digestion, tissue remodeling, and the immune response (Bond, 2019, J Biol Chem). In drug development, the term 'non-target proteases' refers to the broad array of proteolytic enzymes that a candidate drug might inadvertently inhibit, which is a primary source of off-target toxicity and clinical failure (Drag and Salvesen, 2010, Nat Rev Drug Discov). While specific proteases are highly successful therapeutic targets—for instance, in the treatment of HIV/AIDS, hypertension, and type 2 diabetes—achieving high selectivity across the protease family remains a significant challenge (Turk, 2006, Nat Rev Drug Discov). Consequently, this entry describes a functional class of enzymes and a pharmacological concept rather than a single, discrete molecular target.

Other names

PeptidasesProteolytic enzymesHuman degradomeOff-target proteases

Inhibition of proteolytic activity by binding to the catalytic active site or allosteric sites of specific protease enzymes to prevent substrate cleavage.