ICMT Inhibitor-Calbiochem

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一般描述

A cell-permeable indole acetamide that acts as a substrate-competitive and AdoMet-noncompetitive Icmt (isoprenylcysteine carboxyl methyltransferase) inhibitor (K_i= 0.02 ?M; IC₅₀= 0.29 ?M; 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 ?M) 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 limitedin vivoefficacy.
A cell-permeable indole acetamide compound that inhibits Icmt (isoprenylcysteine carboxyl methyltransferase) activity in an acceptor substrate isoprenylated cysteine-competitive (K_i= 0.02 ?M; IC₅₀= 0.29 and 2.1 ?M, 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 ?M) and prevent anchorage-independent growth of colon cancer DKOB8 (by >90% at 20 ?M) in a dose- and Icmt-dependent manner. Cysmethynil (25 ?M) 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 limitedin vivoefficacy (tumor volume on day 28 = 9- and 22-fold of day 0, respectively, with or without 200 mg/kg/i.p. q.o.d.).

包装

10 mg in Glass bottle
Packaged under inert gas

警告

Toxicity: Regulatory Review (Z)

重悬

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C).

其他说明

Go, M.L., et al. 2010.J. Med. Chem.53,6838; Wang, M., et al. 2008.J. Biol. Chem.283,18678; Baron, R.A., et al. 2007.Biochemistry46,554; Winter-Vann, A.M., et al. 2005.Proc. Natl. Acad. Sci. USA102,4336.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

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