Cancer Hydrolase KIAA1363 Inhibitor, JW480

A membrane-permeable carbamate that acts as a highly potent and selective inhibitor against the 2-acetyl MAGE (monoakylglycerol ether) hydrolase KIAA1363/AADACL1 of both human (IC₅₀ = 12 nM; PC3 cell lysate) and murine (IC₅₀ = 20 nM; mouse brain membrane homogenate) origin, presumably via covalent/irreversible carbamoylation of enzyme active site nucleophilic serine, with no significant effect toward other PC3 or murine brain serine hydrolase activities, including HSL, FAAH, and AChE. Readily crosses blood-brain barrier in mice (complete inhibition of brain KIAA1363 in 4 h after single i.p. or o.g./oral gavage dose of 5 mg/kg and 20 mg/kg, respectively). Reported to inhibit the survival of PC3 prostate cancer cells in cultures in vitro (by 34%; 48 h; 1 µM) and suppress PC3-derived tumor growth in mice in vivo (by 56% on day 33; 80 mg/kg/day; o.g.). Also inhibits blood carboxylesterase.

A membrane-permeable, highly potent and selective inhibitor against the 2-acetyl MAGE (monoakylglycerol ether) hydrolase KIAA1363/AADACL1 of both human (IC₅₀ = 12 nM; PC3 lysate) and murine (IC₅₀ = 20 nM; brain membrane samples) origin, with no significant effect toward other PC3 or murine brain serine hydrolase activities, including HSL, FAAH, and AChE. Readily crosses blood-brain barrier in mice and effectively suppresses PC3-derived tumor growth in mice in vivo (by 56% on day 33; 80 mg/kg/day; o.g.). Also inhibits blood carboxylesterase.

Packaged under inert gas

Chang, J.W., et al. 2011. Chem. Biol.18, 476.

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

Toxicity: Regulatory Review (Z)