geranylgeranyltransferase I inhibitor (Merck & Co.)

Geranylgeranyltransferase I inhibitors (GGTIs) are a class of small molecule therapeutics designed to inhibit the enzyme geranylgeranyltransferase I (GGTase I). This enzyme catalyzes the post-translational addition of a 20-carbon geranylgeranyl isoprenoid lipid to the C-terminal cysteine of proteins containing a CAAX motif, where X is typically leucine or isoleucine. This modification, known as geranylgeranylation, is essential for the membrane anchoring and biological activity of numerous signaling proteins, including members of the Rho family (e.g., RhoA, Rac1, Cdc42) and certain Ras-related proteins (e.g., Rap1, RalB). GGTIs disrupt these signaling pathways, leading to G1 phase cell cycle arrest, induction of apoptosis, and inhibition of cell migration and invasion. While many GGTIs like GGTI-298 and P61A6 have been extensively used as research tools to study the role of protein prenylation in cancer and inflammation, some compounds, such as the dual farnesyltransferase and geranylgeranyltransferase inhibitor L-778,123, have advanced into clinical trials for indications like locally advanced pancreatic cancer.

Other names

geranylgeranyltransferase I inhibitorGGTase I inhibitorGGTI