DPPL2 Inhibitors

DPPL2 inhibitors encompass a diverse array of chemical compounds that indirectly impede the enzyme's function by targeting the various biological processes and pathways involved in protein palmitoylation and depalmitoylation. For instance, the availability of palmitoyl-CoA, a crucial substrate for the palmitoylation of proteins, can be diminished by compounds that inhibit enzymes in lipid metabolism or fatty acid synthesis, thereby resulting in a decreased pool of palmitoylated proteins for DPPL2 to act on. Brominated fatty acids and certain natural products inhibit the palmitoylation process itself, further limiting the substrates accessible to DPPL2. Additionally, the use of inhibitors that selectively target related thioesterases can lead to an accumulation of palmitoylated proteins, which may reduce DPPL2's functional capacity by saturating the palmitoylation-depalmitoylation cycle.

Other approaches to inhibit DPPL2 involve altering the composition and processing of membrane proteins, which are significant carriers of palmitoyl modifications. Agents that disrupt protein maturation, such as glycosylation inhibitors, indirectly affect DPPL2's substrate availability by impeding the proper folding and trafficking of proteins that require palmitoylation for their function. Chaperone inhibitors can also play a role in this process by preventing proteins from reaching their functional conformation, thus indirectly reducing the efficacy of DPPL2's action on these misfolded or retained proteins. Furthermore, small molecules that interfere with vesicular transport can lead to a buildup of proteins in the Golgi apparatus or endoplasmic reticulum, limiting the access of these proteins to DPPL2 in cellular locations where depalmitoylation typically occurs.