Post-translational protein prenylation is a 3-step process that occurs at the C-terminus of a number of proteins involved in cell growth control and oncogenesis. Isoprenylcysteine carboxyl methyltransferase (Icmt) catalyzes the methylation of C-terminal prenylcysteine residues, the last step in this process. Cysmethynil is an indole-based, time-dependent inhibitor of Icmt (IC₅₀ = <200 nM).¹ It acts as a competitive inhibitor with respect to the isoprenylated cysteine substrate and a noncompetitive inhibitor with respect to S-adenosylmethionine (K_i = 0.14 µM for the final complex).² It does not inhibit other enzymes in the prenylation pathway (farensyltransferase, geranylgeranyltransferase type I, and Rce1) at concentrations up to 50 µM, or related methyltransferases.¹ Treatment of cancer cells results in a dose-dependent decrease in Ras carboxylmethylation, mislocalization of Ras, and impaired signaling through Ras pathways.¹ Treatment of PC3 prostate cancer cells with 25 µM cysmethynil resulted in decreased mTOR signaling, accumulation of cells in the G₁ phase, and autophagy-mediated cell death.³

≥98%