ZDHHC5 Inhibitors

ZDHHC5 inhibitors broadly encompass molecules that influence the activity of the ZDHHC5 enzyme, which plays a role in protein palmitoylation. Palmitoylation regulates many cellular processes, from protein-protein interactions to subcellular localization. Notably, 2-Bromopalmitate is recognized as a direct inhibitor of DHHC enzymes. Its mechanism stems from its ability to inhibit various DHHC enzymes, protein palmitoylation.

Meanwhile, chemicals like Palmostatin B, ML348, and ML349 take a slightly different route. Instead of directly affecting ZDHHC5, they target enzymes responsible for depalmitoylation (APT1 and APT2). By inhibiting these enzymes, there is a shift in the palmitoylation balance, indirectly influencing ZDHHC5's activity. The availability of palmitate is crucial for the action of ZDHHC5. Chemicals such as Cerulenin and C75, which inhibit fatty acid synthase, influence palmitate synthesis and, consequently, the action of DHHC enzymes. Furthermore, compounds like Tunicamycin and PF-429242 can influence processes that are upstream or related to palmitoylation, adding another layer of regulation. Additionally, modulating lipid metabolism can indirectly impact ZDHHC5. Compounds like Troglitazone, a PPARγ agonist, and BADGP, which affects glycerol-3-phosphate acyltransferase, embody this approach.