GGPS1 (geranylgeranyl diphosphate synthase 1) Inhibitors

The prenyltransferase family consists of enzymes that catalyze the transfer of prenyl groups to various substrates, playing a key role in the post-translational modification of proteins. This family includes farnesyltransferase and geranylgeranyltransferase, which attach farnesyl and geranylgeranyl groups, respectively, to the cysteine residues in specific protein motifs. These lipid modifications are critical for the proper localization and function of a range of proteins, including members of the Ras superfamily. By anchoring proteins to cell membranes, prenylation facilitates their involvement in signal transduction pathways, impacting processes like cell growth, differentiation, and apoptosis. Dysregulation of prenyltransferase activity is linked to various diseases, including cancer and developmental disorders, due to its role in controlling the activity of several oncogenes and signaling molecules. Additionally, prenyltransferases are involved in cholesterol synthesis and other essential metabolic pathways, underscoring their importance in overall cellular function.

Targeting geranylgeranyl diphosphate (GGPP) synthase, which catalyzes the formation of GGPP from farnesyl diphosphate and isopentenyl diphosphate, with small molecules provides valuable insights into the prenylation process. By inhibiting this enzyme, researchers can study the effects of reduced availability of GGPP on protein geranylgeranylation and its subsequent impact on cellular signaling and function. This approach helps in elucidating the role of geranylgeranylated proteins in various cellular processes, including their contribution to disease pathogenesis.