JZL-184

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H24N2O9
Molecular Weight	520.4875
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(C1CCN(CC1)C(=O)OC2=CC=C(C=C2)[N+]([O-])=O)(C3=CC=C4OCOC4=C3)C5=CC=C6OCOC6=C5

InChI

InChIKey=SEGYOKHGGFKMCX-UHFFFAOYSA-N

InChI=1S/C27H24N2O9/c30-26(38-21-5-3-20(4-6-21)29(32)33)28-11-9-17(10-12-28)27(31,18-1-7-22-24(13-18)36-15-34-22)19-2-8-23-25(14-19)37-16-35-23/h1-8,13-14,17,31H,9-12,15-16H2

HIDE SMILES / InChI

Molecular Formula	C27H24N2O9
Molecular Weight	520.4875
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19029917
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/21600985 | http://www.ncbi.nlm.nih.gov/pubmed/23127915

JZL184 is an irreversible inhibitor for monoacylglycerol lipase (MAGL), the primary enzyme responsible for degrading the endocannabinoid 2-arachidonoylglycerol (2-AG). Selectivity of JZL 184 over other serine hydrolases makes it useful compound to study endogenous 2-AG signaling. Administration of JZL184 to mice was reported to cause dramatic elevation of brain 2-AG leading to several cannabinoid-related behavioral effects. JZL184 was found effective in preclinical models of anxiety and chemotherapy-induced neuropathic pain.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Monoglyceride lipase 8 Target ID: CHEMBL4191 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19029917	Inhibitor 8297		8.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Neuropathic pain 26 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23127915	Palliative		Preclinical	Unknown Approved Use Unknown
Anxiety 267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21600985	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects.	2009 Jan	19029917
High-performance liquid chromatography assay with fluorescence detection for the evaluation of inhibitors against human recombinant monoacylglycerol lipase.	2010 Apr 15	20015447
Inhibitors of monoacylglycerol lipase, fatty-acid amide hydrolase and endocannabinoid transport differentially suppress capsaicin-induced behavioral sensitization through peripheral endocannabinoid mechanisms.	2010 Sep	20416378
Effect of developmental chlorpyrifos exposure, on endocannabinoid metabolizing enzymes, in the brain of juvenile rats.	2011 Jul	21507991
Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates.	2012 May 25	22542104
Endogenous 2-Arachidonoylglycerol Alleviates Cyclooxygenases-2 Elevation-Mediated Neuronal Injury From SO2 Inhalation via PPARγ Pathway.	2015 Oct	26209559

Patents

Sample Use Guides

In Vivo Use Guide

JZL184 was dissolved by vortexing, sonicating, and gentle heating directly into 4:1 v/v PEG300:Tween80 (10, 4, 2, or 1 mg ml-1). Male C57Bl/6J mice (6-8 weeks old, 20-26 g) were intraperitoneally (i.p.) administered JZL184 at a volume of 4 ul g-1 weight (40, 16, 8, or 4 mg kg-1 by the dilutions above).

Route of Administration: Intraperitoneal

In Vitro Use Guide

Recombinant MAGL in COS7 cells (0.1 µg) in PBS (200 µl) was incubated with inhibitor at 37C for 30 min. 2-AG (100 µM) was added. Reaction was quenched by the addition of 500 µL 2:1 v/v CHCl3:MeOH, doped with 0.5 nmol PDA, vortexed, then centrifuged (1,400 x g, 3 min) to separate the phases. 30 µl of the resultant organic phase was injected onto an Agilent 1100 series LC-MSD SL instrument. Hydrolysis products were quantified by measuring the area under the peak in comparison to the PDA standard.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 07:59:47 GMT 2023` Edited by `admin` on `Sat Dec 16 07:59:47 GMT 2023`
Record UNII	7MZ1I2J68A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

JZL-184

Common Name

English

1-PIPERIDINECARBOXYLIC ACID, 4-(BIS(1,3-BENZODIOXOL-5-YL)HYDROXYMETHYL)-, 4-NITROPHENYL ESTER

Systematic Name

English

Code System Code Type Description

WIKIPEDIA

JZL184