420350

ICMT Inhibitor

The ICMT Inhibitor controls the biological activity of ICMT. This small molecule/inhibitor is primarily used for Cancer applications.

• Sinonimo/i: ICMT Inhibitor, 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
• Formula empirica (notazione di Hill): C₂₅H₃₂N₂₀
• Peso molecolare: 612.66
• Codice UNSPSC: 12352200
• NACRES: NA.77

Proprietà

• Livello qualitativo: 100
• Saggio: ≥95% (HPLC)
• Forma fisica: semisolid
• Produttore/marchio commerciale: Calbiochem^®
• Condizioni di stoccaggio: OK to freeze; protect from light
• Colore: pale yellow
• Solubilità: DMSO: 100 mg/mL
• Condizioni di spedizione: ambient
• Temperatura di conservazione: −20°C

Descrizione

Descrizione generale

A cell-permeable indole acetamide compound that inhibits Icmt (isoprenylcysteine carboxyl methyltransferase) activity in an acceptor substrate isoprenylated cysteine-competitive (K_i = 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.).

A cell-permeable indole acetamide that acts as a substrate-competitive and AdoMet-noncompetitive Icmt (isoprenylcysteine carboxyl methyltransferase) inhibitor (K_i = 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.

Confezionamento

Packaged under inert gas

Attenzione

Toxicity: Regulatory Review (Z)

Ricostituzione

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

Altre note

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.

Note legali

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

Informazioni sulla sicurezza

• Codice della classe di stoccaggio: 11 - Combustible Solids
• Classe di pericolosità dell'acqua (WGK): WGK 3
• Punto d’infiammabilità (°F): Not applicable
• Punto d’infiammabilità (°C): Not applicable