RHBDL2 Inhibitors

Chemical inhibitors of RHBDL2 include a variety of compounds that target protease activity through different mechanisms. E-64 and its derivative E-64d are potent, irreversible inhibitors that covalently bind to the active site cysteine residue of RHBDL2. This binding blocks substrate access and inhibits proteolytic activity, effectively reducing the protein's function. Similarly, Leupeptin, a reversible inhibitor, targets the active site of RHBDL2 and other serine and cysteine proteases, preventing the cleavage of peptide bonds in substrates, thereby inhibiting the enzyme's activity. AEBSF also acts by covalently modifying the active site of serine proteases like RHBDL2, leading to inhibition of its proteolytic function.

In parallel, some inhibitors exert indirect effects on RHBDL2 by altering the substrate or enzyme availability within the cell. For instance, Pepstatin A, primarily an aspartyl protease inhibitor, can lead to changes in protease networks that result in reduced substrate availability for RHBDL2. Chymostatin, a chymotrypsin inhibitor, can modify protease cascades, indirectly affecting RHBDL2's interaction with substrates. Proteasome inhibitors like MG132 and Lactacystin induce the accumulation of ubiquitinated proteins, which may sequester RHBDL2 and indirectly inhibit its function due to increased competition for substrates. ALLN, while a calpain inhibitor, can also inhibit cysteine proteases and thus potentially block RHBDL2's active site. Z-VAD-FMK, a pan-caspase inhibitor known to irreversibly bind to the cysteine active site, can inhibit RHBDL2 and other cysteine proteases. Aprotinin, although a small protein inhibitor, can inhibit several proteolytic enzymes and may reduce RHBDL2 activity through competitive inhibition. Lastly, Marimastat, a broad-spectrum inhibitor of matrix metalloproteases, can indirectly inhibit RHBDL2 by affecting the extracellular matrix remodeling, potentially impacting the protein's accessibility to its substrates.