ICMT Inhibitor – Calbiochem

Descrição detalhada : A cell-permeable indole acetamide that acts as a substrate-competitive and AdoMet-noncompetitive Icmt (isoprenylcysteine carboxyl methyltransferase) inhibitor (Ki = 0.02 µM; IC50 = 0.29 µM; Substrate = S-farnesyl-L-cysteine), exhibiting no activity against FTase, gernaylgeranyltransferase type I, CaaX protease Rce1, AdoMet-dependent DNA methyltransferase, SssI DNA methyltransferase, or PCMT1 protein methyltransferase. Cysmethynil (25 µM) induces G1 cell cycle-arrest and autophagy-mediated, but not apoptotic, cell death in prostate cancer PC3 cells with concomitant PI 3-K/Akt and mTOR signaling blockage, consistent with inhibition of Icmt-mediated activation of Ras and Rheb GTPases. Murine PC3 xenograft studies reveal limited in vivo efficacy., A cell-permeable indole acetamide compound that inhibits Icmt (isoprenylcysteine carboxyl methyltransferase) activity in an acceptor substrate isoprenylated cysteine-competitive (Ki = 0.02 µM; IC50 = 0.29 and 2.1 µM, respectively, with or without inhibitor preincubation; Substrate = S-farnesyl-L-cysteine) and donor substrate AdoMet-noncompetitive manner, exhibiting no activity against FTase, gernaylgeranyltransferase type I, CaaX protease Rce1, AdoMet-dependent DNA methyltransferase, SssI DNA methyltransferase, or PCMT1 protein methyltransferase. Shown to inhibit the proliferation of non-cancer MEF cells (by 100% at 30 µM) and prevent anchorage-independent growth of colon cancer DKOB8 (by >90% at 20 µM) in a dose- and Icmt-dependent manner. Cysmethynil (25 µM) induces G1 cell cycle-arrest and autophagy-mediated, but not apoptotic, cell death in prostate cancer PC3 cells with concomitant PI 3-K/Akt and mTOR signaling blockage, consistent with inhibition of Icmt-mediated activation of Ras and Rheb GTPases. Murine PC3 xenograft studies reveal limited in vivo efficacy (tumor volume on day 28 = 9- and 22-fold of day 0, respectively, with or without 200 mg/kg/i.p. q.o.d.).
Sinónimos : ICMT Inhibitor - Calbiochem; 2-(5-(3-Methylphenyl)-1-octyl-1H-indol-3-yl)acetamide, 2-(1-Octyl-5-m-tolyl-1H-indol-3-yl) acetamide, Cysmethynil, Cysmethynil, Isoprenylcysteine Carboxyl Methyltransferase Inhibitor
Fórmula molecula r: C25H32N20
Armazenamento : -20C
Embalagem : 1X10MG