Recent advances in patented inhibitors targeting serine proteases in inflammatory diseases

Serine proteases are critical enzymes involved in various physiological and pathological processes, particularly inflammation. Recent years have seen a great increase in the patenting of serine protease's inhibitors as therapeutic strategies for inflammatory disorders with highly significant clinical translation. Serine protease inhibitors represent indeed a very active therapeutical area in many leading pathologies with inflammatory components such as vascular diseases, skin inflammation, respiratory or neurodegenerative diseases. In this review, we give an overview on targeted strategies, diversity of the chemical structures of inhibitors, significant disease applications e.g. most significant examples in the period (2017-early 2025) which includes inhibitors of plasma kallikrein, kallikrein-related peptidases, plasmin, factors XI and XII, and HtrA serine proteases. Over 60 patents have been filled during the investigated period covering nanomolar small-molecule inhibitors with varied heterocyclic structures or cyclic peptides either targeting active site or exosites. In addition, several therapeutical antibodies including bispecific antibodies or nanobodies have been also developed, some of them are already in advanced clinical trials.