1101854-58-3 Usage
Description
Endocannabinoids such as 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide (AEA) are biologically active lipids that are involved in a number of synaptic processes including activation of cannabinoid receptors. Monoacylglycerol lipase (MAGL) is a serine hydrolase responsible for the hydrolysis of 2-AG to arachidonic acid and glycerol, thus terminating its biological function. JZL 184 is a potent and selective inhibitor of monoacylglycerol lipase (MAGL) that displays IC50 values of 8 nM and 4 μM for inhibition of MAGL and fatty acid amide hydrolase in mouse brain membranes, respectively. When administered to mice at 16 mg/kg, intraperitoneally, JZL 184 reduces MAGL activity by 85%, elevates brain 2-AG levels by 8-fold, and elicits analgesic activity in a variety of pain assays that qualitatively mimics direct central cannabinoid (CB1) agonists.
Uses
Different sources of media describe the Uses of 1101854-58-3 differently. You can refer to the following data:
1. JZL 184 hydrate has been used as an inhibitor of monoacylglycerol lipase to study its effect on human osteoblast differentiation and proliferation and postsynaptic neurons.
2. JZL184 is a strong and selective inhibitor of Monoglyceride Lipase.
Biochem/physiol Actions
JZL184 selectively inhibits MAGL, the enzyme predominantly responsible for the degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG). Anandamide and 2-AG are the two endogenous endocannabinoids that activate the cannabinoid receptors CB1 and CB2. Anandamide is predominantly metabolized by fatty acid amide hydrolase (FAAH), whereas monoacylglycerol lipase (MAGL) is thought to be the enzyme primarily responsible for the degradation of 2-AG. It is difficult to separate the activities of the two because most currently available inhibitors of MAGL are not selective, and also inhibit FAAH or other enzymes. JZL 184 is the first selective inhibitor of MAGL with nanomolar portency and over 200-fold selectivity for MAGL vs FAAH. When administered to mice, JZL184 increased levels of 2-arachidonoylglycerol in the brain by about 8-fold, with no effect on levels of anandamide.
References
1) Long et al. (2009), Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects; Nat. Chem. Biol.,5 37
2) Pan et al. (2009), Blockade of 2-arachidonoylglycerol hydrolysis by selective monoacylglycerol lipase inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxyl)methyl)piperidine-1-carboxylate (JZL 184) enhances retrograde endocannabinoid signaling; J. Pharmacol. Exp. Ther., 331 591
3) Kinsey et al. (2009), Blockade of endocannabinoid-degrading enzymes attenuates neuropathic pain; J. Pharmacol. Exp. Ther., 330 902
Check Digit Verification of cas no
The CAS Registry Mumber 1101854-58-3 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,1,0,1,8,5 and 4 respectively; the second part has 2 digits, 5 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1101854-58:
(9*1)+(8*1)+(7*0)+(6*1)+(5*8)+(4*5)+(3*4)+(2*5)+(1*8)=113
113 % 10 = 3
So 1101854-58-3 is a valid CAS Registry Number.
