Cysmethynil is a selective small-molecule inhibitor of tisoprenylcysteine carboxyl methyltransferase (Icmt) with IC50 <200 nM.
Cysmethynil does not inhibit other enzymes (farensyltransferase, geranylgeranyltransferase type I, and Rce1) at concentrations up to 50 uM.
Cysmethynil acts as a competitive inhibitor with respect to the isoprenylated cysteine substrate and a noncompetitive inhibitor with respect to S-adenosylmethionine (Ki=0.14 uM).
Cysmethynil causes decrease in Ras carboxylmethylation, mislocalization of Ras, and impaired signaling through Ras pathways, reduces mTOR signaling and results in both an accumulation of cells in the G(1) phase and cell death in PC3 cells.
Physicochemical Properties
M.Wt
376.5
Formula
C25H32N2O
Appearance
Solid
CAS No.
Storage
Solide Powder
-20 °C 12 Months; 4°C 6 Months
In Solvent
-80 °C 6 Months; -20°C 6 Months
Shipping
Solubility
10 mM in DMSO
Chemical Name/SMILES
5-(3-Methylphenyl)-1-octyl-1H-indole-3-acetamide
References
1. Winter-Vann AM, et al. Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4336-41.
2. Baron RA, et al. Biochemistry. 2007 Jan 16;46(2):554-60.
3. Wang M, et al. J Biol Chem. 2008 Jul 4;283(27):18678-84.
