USP44 Inhibitors

USP44 Inhibitors primarily consists of molecules that target deubiquitinating enzymes (DUBs) and the ubiquitin-proteasome system, albeit indirectly. This category can be divided into several subtypes, each with a unique mechanism of action. For instance, compounds like N-ethylmaleimide (NEM) and PR-619 target the active sites of a broad range of DUBs, thereby affecting USP44. These chemicals react with the cysteine residues in the enzymes' active sites, disrupting their ability to cleave ubiquitin from substrate proteins. Meanwhile, compounds such as MG-132, Bortezomib, and Epoxomicin act as proteasome inhibitors. They interfere with proteasome-associated deubiquitinase activity, creating an environment where USP44 is less effective. This approach affects the enzyme's physiological role without directly binding to it.

Another interesting group within this class is compounds like Ubistatins, which disrupt the binding of ubiquitin to various proteins. By inhibiting ubiquitin binding, they indirectly limit the substrates available for USP44 to act upon. Also noteworthy are chemicals like ML323, LDN-57444, and IU1, which target closely related DUBs or ubiquitin isopeptidase activity. These chemicals can inhibit USP44 by competitive inhibition or by modulating the shared ubiquitin-proteasome system. Overall, USP44 Inhibitors operate through a variety of mechanisms, either by directly affecting DUBs or by influencing the broader cellular pathways where USP44 functions. Each approach offers a distinct way to modulate the enzyme's activity, making this class versatile in affecting the biochemical role of USP44.