JZL 184 Chemical Properties

Melting point:

116-120°C

Boiling point:

706.4±60.0 °C(Predicted)

Density 

1.467±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Soluble in DMSO (up to 25 mg/ml).

form 

White to off-white solid

pka

13.32±0.29(Predicted)

color 

light yellow to yellow-green

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months

CAS DataBase Reference

1101854-58-3

Safety Information

RIDADR 

UN 2811 6.1 / PGIII

HS Code 

29349990

JZL 184 Usage And Synthesis

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

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.

Uses

JZL184 is a strong and selective inhibitor of Monoglyceride Lipase.

Definition

ChEBI: 4-[bis(1,3-benzodioxol-5-yl)-hydroxymethyl]-1-piperidinecarboxylic acid (4-nitrophenyl) ester is a member of benzodioxoles.

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.

storage

Store at -20°C

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

JZL 184(1101854-58-3)Related Product Information

• (E)-3-[[[3-[2-(7-CHLORO-2-QUINOLINYL)ETHENYL]PHENYL]-[[(3-DIMETHYLAMINO)-3-OXOPROPYL]THIO]METHYL]THIO]-PROPANOIC ACID, SODIUM SALT
• Fatostatin A
• N-(1-OXO-4Z,7Z,10Z,13Z,16Z,19Z-DOCOSAHEXAENYL)-GLYCINE
• PF-622
• N-Arachidonyl maleimide
• Bortezomib
• Tiotropium bromide hydrate
• URB597
• OTX015
• PD 0332991 HCl
• BEZ235 (NVP-BEZ235, Dactolisib)