JZL195   

GtoPdb Ligand ID: 8606

Synonyms: JZL 195 | JZL-195
Compound class: Synthetic organic
Comment: JZL195 was first reported as a dual inhibitor of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGLL, a.k.a. MAGL) in 2009 [5]. Animal experiments suggest that dual FAAH/MAGL inhibitiors may have improved analgesic effects against neuropathic pain, in comparison to selective FAAH and MAGL inhibitors, or cannabinoid receptor agonists [1-2,4,6].
JZL195 has since been reported to also inhibit acyloxyacyl hydrolase (AOAH) [3]
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 3
Hydrogen bond donors 0
Rotatable bonds 8
Topological polar surface area 85.15
Molecular weight 433.16
XLogP 4.32
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES O=C(N1CCN(CC1)Cc1cccc(c1)Oc1ccccc1)Oc1ccc(cc1)[N+](=O)[O-]
Isomeric SMILES O=C(N1CCN(CC1)Cc1cccc(c1)Oc1ccccc1)Oc1ccc(cc1)[N+](=O)[O-]
InChI InChI=1S/C24H23N3O5/c28-24(32-22-11-9-20(10-12-22)27(29)30)26-15-13-25(14-16-26)18-19-5-4-8-23(17-19)31-21-6-2-1-3-7-21/h1-12,17H,13-16,18H2
InChI Key QNYRAEKLMNDRFY-UHFFFAOYSA-N
References
1. Adamson Barnes NS, Mitchell VA, Kazantzis NP, Vaughan CW. (2016)
Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model.
Br. J. Pharmacol., 173 (1): 77-87. [PMID:26398331]
2. Anderson WB, Gould MJ, Torres RD, Mitchell VA, Vaughan CW. (2014)
Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine inflammatory pain model.
Neuropharmacology, 81: 224-30. [PMID:24384256]
3. Bachovchin DA, Koblan LW, Wu W, Liu Y, Li Y, Zhao P, Woznica I, Shu Y, Lai JH, Poplawski SE et al.. (2014)
A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity.
Nat. Chem. Biol., 10 (8): 656-63. [PMID:24997602]
4. Ghosh S, Kinsey SG, Liu QS, Hruba L, McMahon LR, Grim TW, Merritt CR, Wise LE, Abdullah RA, Selley DE et al.. (2015)
Full Fatty Acid Amide Hydrolase Inhibition Combined with Partial Monoacylglycerol Lipase Inhibition: Augmented and Sustained Antinociceptive Effects with Reduced Cannabimimetic Side Effects in Mice.
J. Pharmacol. Exp. Ther., 354 (2): 111-20. [PMID:25998048]
5. Long JZ, Nomura DK, Vann RE, Walentiny DM, Booker L, Jin X, Burston JJ, Sim-Selley LJ, Lichtman AH, Wiley JL et al.. (2009)
Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo.
Proc. Natl. Acad. Sci. U.S.A., 106 (48): 20270-5. [PMID:19918051]
6. Sakin YS, Dogrul A, Ilkaya F, Seyrek M, Ulas UH, Gulsen M, Bagci S. (2015)
The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.
Neurogastroenterol. Motil., 27 (7): 936-44. [PMID:25869205]