A mini review of small-molecule inhibitors targeting palmitoyltransferases

Abstract

Palmitoylation occurs when fatty acids (such as palmitic acid) create covalent bonds between cysteine, serine, threonine, or other residues in proteins. The downstream effect of palmitoylation depends on the protein being palmitoylated because its blockage can render the protein useless in terms of its physiological function. Based on this, modulating the palmitoylation process becomes a good strategy for influencing cell proliferation, differentiation, metabolism, and apoptosis, allowing diabetes, obesity, and even cancer to be efficiently treated. As a determinant of the palmitoylation process, palmitoyltransferase is defined as an enzyme that catalyzes the transfer of the palmitate groups from Self-palmitoylated palmitoyl coenzyme A to another substrate. When it comes to the three most commonly cited palmitoyltransferases, serine palmitoyltransferase (SPT), carnitine palmitoyltransferase (CPT), and protein palmitoyltransferase (PAT), some similarities were found in the procedures by which they function, and in the structures of the small-molecule drugs that inhibit them. For this reason, we introduce the three above-mentioned palmitoyltransferases and describe the development of small molecule inhibitors for them to provide inspiration for the discovery of palmitoyltransferase inhibitors.

Keywords

• Inhibitors
• Serine palmitoyltransferase
• Carnitine palmitoyltransferase
• Protein palmitoyltransferase