PSMD5 Inhibitors

The class of chemicals known as PSMD5 inhibitors encompasses compounds that interfere with the functional components of the proteasome, a protein complex responsible for degrading unwanted or misfolded proteins through the ubiquitin-proteasome system. PSMD5 is a non-ATPase subunit of the 19S regulatory particle within the 26S proteasome. It is involved in recognizing ubiquitinated protein substrates and presenting them to the 20S core particle for degradation. The inhibitors listed act indirectly on PSMD5 by targeting the proteolytic activity of the proteasome complex.

These inhibitors are primarily composed of compounds that bind to the catalytic sites of the proteasome. For example, Bortezomib and Carfilzomib are part of a class known as peptide boronates, which reversibly and irreversibly inhibit the proteasome, respectively. Lactacystin and Salinosporamide A are β-lactone-related inhibitors that irreversibly bind to the proteasome's active site. Epoxyketones such as Epoxomicin and PI-1840 also target the proteasome's active site but do so with a different binding mechanism. These chemicals can lead to the accumulation of ubiquitinated proteins, which in turn hampers the proteasomal function and indirectly affects the activity of regulatory subunits like PSMD5. With the proteasome unable to perform its function effectively, PSMD5 is also rendered less effective as part of the regulatory complex. The impairment of the proteasome's proteolytic activities by these chemicals results in an overall inhibition of the protein degradation process, which PSMD5 facilitates. The diversity of these inhibitors reflects the range of mechanisms by which the proteasome's function can be modulated