WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 510320
CAS#: 1101854-58-3
Description: JZL184 is highly selective, and potent MAGL inhibitor ( monoacylglycerol lipase inhibitor). JZL184 improves behavior and neural properties in Ts65Dn mice, a model of down syndrome. JZL184 attenuates LPS-induced increases in cytokine expression in the rat frontal cortex and plasma: differential mechanisms of action. JZL184 also suppresses inflammatory pain in the mouse carrageenan model.
MedKoo Cat#: 510320
Name: JZL184
CAS#: 1101854-58-3
Chemical Formula: C27H24N2O9
Exact Mass: 520.1482
Molecular Weight: 520.494
Elemental Analysis: C, 62.30; H, 4.65; N, 5.38; O, 27.67
Synonym: JZL184; JZL 184; JZL-184.
IUPAC/Chemical Name: 4-nitrophenyl 4-(bis(benzo[d][1,3]dioxol-5-yl)(hydroxy)methyl)piperidine-1-carboxylate.
InChi Key: SEGYOKHGGFKMCX-UHFFFAOYSA-N
InChi Code: 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
SMILES Code: O=C(N1CCC(C(C2=CC=C(OCO3)C3=C2)(C4=CC=C(OCO5)C5=C4)O)CC1)OC6=CC=C([N+]([O-])=O)C=C6
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | JZL 184 is a potent, selective and irreversible MAGL inhibitor that blocks 2-Arachidonoylglycerol (2-AG) hydrolysis in brain membranes (IC50 of 8 nM). JZL 184 displays >300-fold selectivity for MAGL over FAAH. |
| In vitro activity: | In vitro, JZL184 induced a time- and concentration-dependent reduction of A549 cell invasion through Matrigel-coated membranes, which was likewise reversed by AM-251. Reference: Mol Cancer Ther. 2021 May;20(5):787-802. https://pubmed.ncbi.nlm.nih.gov/33632876/ |
| In vivo activity: | Mice given daily injections of high-dose JZL184 (≥16 mg/kg) for 6 days displayed decreased CB1 receptor density and function in the brain, as assessed in [(3)H]SR141716A binding and CP55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol]-stimulated guanosine 5'-O-(3-[(35)S]thio)triphosphate binding assays, respectively. In contrast, normal CB1 receptor expression and function were maintained following repeated administration of low-dose JZL184 (≤8 mg/kg). Reference: J Pharmacol Exp Ther. 2013 Jun;345(3):492-501. https://pubmed.ncbi.nlm.nih.gov/23412396/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 30.0 | 57.64 | |
| DMSO | 54.02 | 103.78 |
The following data is based on the product molecular weight 520.494 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Prüser JL, Ramer R, Wittig F, Ivanov I, Merkord J, Hinz B. The Monoacylglycerol Lipase Inhibitor JZL184 Inhibits Lung Cancer Cell Invasion and Metastasis via the CB1 Cannabinoid Receptor. doi: 10.1158/1535-7163.MCT-20-0589. Epub 2021 Feb 25. PMID: 33632876. 2. Ma M, Bai J, Ling Y, Chang W, Xie G, Li R, Wang G, Tao K. Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells. Mol Med Rep. 2016 Mar;13(3):2850-6. doi: 10.3892/mmr.2016.4829. Epub 2016 Jan 29. PMID: 26847687. 3. Kinsey SG, Wise LE, Ramesh D, Abdullah R, Selley DE, Cravatt BF, Lichtman AH. Repeated low-dose administration of the monoacylglycerol lipase inhibitor JZL184 retains cannabinoid receptor type 1-mediated antinociceptive and gastroprotective effects. J Pharmacol Exp Ther. 2013 Jun;345(3):492-501. doi: 10.1124/jpet.112.201426. Epub 2013 Feb 14. PMID: 23412396; PMCID: PMC3657109. 4. Long JZ, Li W, Booker L, Burston JJ, Kinsey SG, Schlosburg JE, Pavón FJ, Serrano AM, Selley DE, Parsons LH, Lichtman AH, Cravatt BF. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol. 2009 Jan;5(1):37-44. doi: 10.1038/nchembio.129. Epub 2008 Nov 23. PMID: 19029917; PMCID: PMC2605181. |
| In vitro protocol: | 1. Prüser JL, Ramer R, Wittig F, Ivanov I, Merkord J, Hinz B. The Monoacylglycerol Lipase Inhibitor JZL184 Inhibits Lung Cancer Cell Invasion and Metastasis via the CB1 Cannabinoid Receptor. doi: 10.1158/1535-7163.MCT-20-0589. Epub 2021 Feb 25. PMID: 33632876. 2. Ma M, Bai J, Ling Y, Chang W, Xie G, Li R, Wang G, Tao K. Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells. Mol Med Rep. 2016 Mar;13(3):2850-6. doi: 10.3892/mmr.2016.4829. Epub 2016 Jan 29. PMID: 26847687. |
| In vivo protocol: | 1. Kinsey SG, Wise LE, Ramesh D, Abdullah R, Selley DE, Cravatt BF, Lichtman AH. Repeated low-dose administration of the monoacylglycerol lipase inhibitor JZL184 retains cannabinoid receptor type 1-mediated antinociceptive and gastroprotective effects. J Pharmacol Exp Ther. 2013 Jun;345(3):492-501. doi: 10.1124/jpet.112.201426. Epub 2013 Feb 14. PMID: 23412396; PMCID: PMC3657109. 2. Long JZ, Li W, Booker L, Burston JJ, Kinsey SG, Schlosburg JE, Pavón FJ, Serrano AM, Selley DE, Parsons LH, Lichtman AH, Cravatt BF. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat Chem Biol. 2009 Jan;5(1):37-44. doi: 10.1038/nchembio.129. Epub 2008 Nov 23. PMID: 19029917; PMCID: PMC2605181. |
1: Lysenko LV, Kim J, Henry C, Tyrtyshnaia A, Kohnz RA, Madamba F, Simon GM, Kleschevnikova NE, Nomura DK, Ezekowitz RA, Kleschevnikov AM. Monoacylglycerol Lipase Inhibitor JZL184 Improves Behavior and Neural Properties in Ts65Dn Mice, a Model of Down Syndrome. PLoS One. 2014 Dec 4;9(12):e114521. doi: 10.1371/journal.pone.0114521. eCollection 2014. PubMed PMID: 25474204.
2: Khasabova IA, Yao X, Paz J, Lewandowski CT, Lindberg AE, Coicou L, Burlakova N, Simone DA, Seybold VS. JZL184 is anti-hyperalgesic in a murine model of cisplatin-induced peripheral neuropathy. Pharmacol Res. 2014 Oct 7;90C:67-75. doi: 10.1016/j.phrs.2014.09.008. [Epub ahead of print] PubMed PMID: 25304184.
3: Ma L, Wang L, Yang F, Meng XD, Wu C, Ma H, Jiang W. Disease-modifying effects of RHC80267 and JZL184 in a pilocarpine mouse model of temporal lobe epilepsy. CNS Neurosci Ther. 2014 Oct;20(10):905-15. doi: 10.1111/cns.12302. Epub 2014 Jul 3. PubMed PMID: 24989980.
4: Fernández-Suárez D, Celorrio M, Riezu-Boj JI, Ugarte A, Pacheco R, González H, Oyarzabal J, Hillard CJ, Franco R, Aymerich MS. The monoacylglycerol lipase inhibitor JZL184 is neuroprotective and alters glial cell phenotype in the chronic MPTP mouse model. Neurobiol Aging. 2014 Nov;35(11):2603-16. doi: 10.1016/j.neurobiolaging.2014.05.021. Epub 2014 May 28. PubMed PMID: 24973119.
5: Seillier A, Dominguez Aguilar D, Giuffrida A. The dual FAAH/MAGL inhibitor JZL195 has enhanced effects on endocannabinoid transmission and motor behavior in rats as compared to those of the MAGL inhibitor JZL184. Pharmacol Biochem Behav. 2014 Sep;124:153-9. doi: 10.1016/j.pbb.2014.05.022. Epub 2014 Jun 6. PubMed PMID: 24911644; PubMed Central PMCID: PMC4150743.
6: Kinsey SG, Wise LE, Ramesh D, Abdullah R, Selley DE, Cravatt BF, Lichtman AH. Repeated low-dose administration of the monoacylglycerol lipase inhibitor JZL184 retains cannabinoid receptor type 1-mediated antinociceptive and gastroprotective effects. J Pharmacol Exp Ther. 2013 Jun;345(3):492-501. doi: 10.1124/jpet.112.201426. Epub 2013 Feb 14. PubMed PMID: 23412396; PubMed Central PMCID: PMC3657109.
7: Kerr DM, Harhen B, Okine BN, Egan LJ, Finn DP, Roche M. The monoacylglycerol lipase inhibitor JZL184 attenuates LPS-induced increases in cytokine expression in the rat frontal cortex and plasma: differential mechanisms of action. Br J Pharmacol. 2013 Jun;169(4):808-19. doi: 10.1111/j.1476-5381.2012.02237.x. PubMed PMID: 23043675; PubMed Central PMCID: PMC3687661.
8: Crow JA, Bittles V, Borazjani A, Potter PM, Ross MK. Covalent inhibition of recombinant human carboxylesterase 1 and 2 and monoacylglycerol lipase by the carbamates JZL184 and URB597. Biochem Pharmacol. 2012 Nov 1;84(9):1215-22. doi: 10.1016/j.bcp.2012.08.017. Epub 2012 Aug 27. PubMed PMID: 22943979; PubMed Central PMCID: PMC3470872.
9: Woodhams SG, Wong A, Barrett DA, Bennett AJ, Chapman V, Alexander SP. Spinal administration of the monoacylglycerol lipase inhibitor JZL184 produces robust inhibitory effects on nociceptive processing and the development of central sensitization in the rat. Br J Pharmacol. 2012 Dec;167(8):1609-19. doi: 10.1111/j.1476-5381.2012.02179.x. PubMed PMID: 22924700; PubMed Central PMCID: PMC3525864.
10: Ghosh S, Wise LE, Chen Y, Gujjar R, Mahadevan A, Cravatt BF, Lichtman AH. The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model. Life Sci. 2013 Mar 19;92(8-9):498-505. doi: 10.1016/j.lfs.2012.06.020. Epub 2012 Jun 28. PubMed PMID: 22749865; PubMed Central PMCID: PMC3717616.
11: Sciolino NR, Zhou W, Hohmann AG. Enhancement of endocannabinoid signaling with JZL184, an inhibitor of the 2-arachidonoylglycerol hydrolyzing enzyme monoacylglycerol lipase, produces anxiolytic effects under conditions of high environmental aversiveness in rats. Pharmacol Res. 2011 Sep;64(3):226-34. doi: 10.1016/j.phrs.2011.04.010. Epub 2011 May 11. PubMed PMID: 21600985; PubMed Central PMCID: PMC3140828.
12: Björklund E, Norén E, Nilsson J, Fowler CJ. Inhibition of monoacylglycerol lipase by troglitazone, N-arachidonoyl dopamine and the irreversible inhibitor JZL184: comparison of two different assays. Br J Pharmacol. 2010 Dec;161(7):1512-26. doi: 10.1111/j.1476-5381.2010.00974.x. PubMed PMID: 20735405; PubMed Central PMCID: PMC3010564.
13: Pan B, Wang W, Long JZ, Sun D, Hillard CJ, Cravatt BF, Liu QS. Blockade of 2-arachidonoylglycerol hydrolysis by selective monoacylglycerol lipase inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) Enhances retrograde endocannabinoid signaling. J Pharmacol Exp Ther. 2009 Nov;331(2):591-7. doi: 10.1124/jpet.109.158162. Epub 2009 Aug 7. PubMed PMID: 19666749; PubMed Central PMCID: PMC2775254.
