Recent insights of PROTAC developments in inflammation-mediated and autoimmune targets: a critical review

Abstract

According to the mounting evidence in the literature, pro-inflammatory mediators/targets activate multiple signalling pathways to trigger illnesses that are ultimately responsible for acute pain, chronic inflammatory diseases, and several auto-immune disorders. Conventional drugs have been ruled out since proteolysis-targeting chimeras (PROTACs) are poised to overcome the limitations of traditional therapies. These heterobifunctional molecules help to degrade the targeted proteins of interest through ubiquitination. This review encompasses current and future aspects of PROTACs in inflammation-mediated and autoimmune targets. Different key points are highlighted and discussed, such as why PROTACs are preferred in this disease area, drawbacks and lessons learnt from the past, the role of linkers in establishing crucial degradation, in vitro findings, pharmacokinetics, in silico parameters, limitations of PROTACs in clinical settings, and future outcomes.