JZL195 | CAS#1210004-12-8 | FAAH/MAGL inhibitor

MedKoo Cat#: 522417 | Name: JZL195

Description:

WARNING: This product is for research use only, not for human or veterinary use.

JZL195 is a potent and selective dual inhibitor of FAAH and monacylglycerol lipase (MAGL). JZL195 has greater anti-allodynic efficacy than selective FAAH, or MAGL inhibitors, plus a greater therapeutic window than a cannabinoid receptor agonist. JZL195 may have greater potential in alleviating neuropathic pain, compared to selective FAAH and MAGL inhibitors, or cannabinoid receptor agonists.

Chemical Structure

JZL195

CAS#1210004-12-8

Theoretical Analysis

MedKoo Cat#: 522417

Name: JZL195

CAS#: 1210004-12-8

Chemical Formula: C24H23N3O5

Exact Mass: 433.1638

Molecular Weight: 433.46

Elemental Analysis: C, 66.50; H, 5.35; N, 9.69; O, 18.45

Price and Availability

Size	Price	Availability
50mg	USD 250.00	2 Weeks
100mg	USD 450.00	2 Weeks
200mg	USD 750.00	2 Weeks
500mg	USD 1,250.00	2 Weeks
1g	USD 1,950.00	2 Weeks
2g	USD 2,950.00	2 Weeks

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Related CAS #

No Data

Synonym

JZL195; JZL-195; JZL 195.

IUPAC/Chemical Name

4-nitrophenyl 4-(3-phenoxybenzyl)piperazine-1-carboxylate

InChi Key

QNYRAEKLMNDRFY-UHFFFAOYSA-N

InChi Code

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

SMILES Code

O=C(N1CCN(CC2=CC=CC(OC3=CC=CC=C3)=C2)CC1)OC4=CC=C([N+]([O-])=O)C=C4

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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

JZL195 is a selective and efficacious dual fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitor with IC50s of 2 and 4 nM, respectively.

In vitro activity:

TBD

In vivo activity:

The effect of systemic injections of a range of doses of JZL195 and the pan-cannabinoid receptor agonist WIN55212 were performed 1 day following intraplantar injection of CFA in C57BL/6 mice. JZL195 and WIN55212 both reduced mechanical allodynia and thermal hyperalgesia, and produced catalepsy and sedation in a dose dependent manner. These findings suggest that JZL195 reduces inflammation induced allodynia at doses below those which produce side-effects, and displays greater efficacy that FAAH or MAGL inhibitors. Thus, dual FAAH/MAGL inhibition has the potential to alleviate inflammatory pain with reduced cannabinoid-like side-effects. Reference: Neuropharmacology. 2014 Jun;81:224-30. https://pubmed.ncbi.nlm.nih.gov/24384256/

	Solvent	mg/mL	mM
Solubility
	DMF	5.0	0.46
	DMSO	29.0	66.86

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 433.46 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. Anderson WB, Gould MJ, Torres RD, Mitchell VA, Vaughan CW. Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine inflammatory pain model. Neuropharmacology. 2014 Jun;81:224-30. doi: 10.1016/j.neuropharm.2013.12.018. Epub 2013 Dec 30. PMID: 24384256. 2. Wise LE, Long KA, Abdullah RA, Long JZ, Cravatt BF, Lichtman AH. Dual fatty acid amide hydrolase and monoacylglycerol lipase blockade produces THC-like Morris water maze deficits in mice. ACS Chem Neurosci. 2012 May 16;3(5):369-78. doi: 10.1021/cn200130s. Epub 2012 Jan 27. PMID: 22860205; PMCID: PMC3382457.

In vitro protocol:

TBD

In vivo protocol:

1: Adamson Barnes NS, Mitchell VA, Kazantzis NP, Vaughan CW. Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine neuropathic pain model. Br J Pharmacol. 2015 Sep 23. doi: 10.1111/bph.13337. [Epub ahead of print] PubMed PMID: 26398331. 2: Manduca A, Morena M, Campolongo P, Servadio M, Palmery M, Trabace L, Hill MN, Vanderschuren LJ, Cuomo V, Trezza V. Distinct roles of the endocannabinoids anandamide and 2-arachidonoylglycerol in social behavior and emotionality at different developmental ages in rats. Eur Neuropsychopharmacol. 2015 Aug;25(8):1362-74. doi: 10.1016/j.euroneuro.2015.04.005. Epub 2015 Apr 14. PubMed PMID: 25914159. 3: Hruba L, Seillier A, Zaki A, Cravatt BF, Lichtman AH, Giuffrida A, McMahon LR. Simultaneous inhibition of fatty acid amide hydrolase and monoacylglycerol lipase shares discriminative stimulus effects with Δ9-tetrahydrocannabinol in mice. J Pharmacol Exp Ther. 2015 May;353(2):261-8. doi: 10.1124/jpet.115.222836. Epub 2015 Feb 24. PubMed PMID: 25711338; PubMed Central PMCID: PMC4407717. 4: Walentiny DM, Vann RE, Wiley JL. Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice. Neuropharmacology. 2015 Jun;93:237-42. doi: 10.1016/j.neuropharm.2015.02.004. Epub 2015 Feb 16. PubMed PMID: 25698527; PubMed Central PMCID: PMC4387086. 5: Belluomo I, Matias I, Pernègre C, Marsicano G, Chaouloff F. Opposite control of frontocortical 2-arachidonoylglycerol turnover rate by cannabinoid type-1 receptors located on glutamatergic neurons and on astrocytes. J Neurochem. 2015 Apr;133(1):26-37. doi: 10.1111/jnc.13044. Epub 2015 Feb 25. PubMed PMID: 25626460. 6: Lau BK, Drew GM, Mitchell VA, Vaughan CW. Endocannabinoid modulation by FAAH and monoacylglycerol lipase within the analgesic circuitry of the periaqueductal grey. Br J Pharmacol. 2014 Dec;171(23):5225-36. doi: 10.1111/bph.12839. Epub 2014 Sep 5. PubMed PMID: 25041240; PubMed Central PMCID: PMC4294036. 7: Bachovchin DA, Koblan LW, Wu W, Liu Y, Li Y, Zhao P, Woznica I, Shu Y, Lai JH, Poplawski SE, Kiritsy CP, Healey SE, DiMare M, Sanford DG, Munford RS, Bachovchin WW, Golub TR. A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity. Nat Chem Biol. 2014 Aug;10(8):656-63. doi: 10.1038/nchembio.1578. Epub 2014 Jul 6. PubMed PMID: 24997602. 8: 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. 9: Anderson WB, Gould MJ, Torres RD, Mitchell VA, Vaughan CW. Actions of the dual FAAH/MAGL inhibitor JZL195 in a murine inflammatory pain model. Neuropharmacology. 2014 Jun;81:224-30. doi: 10.1016/j.neuropharm.2013.12.018. Epub 2013 Dec 30. PubMed PMID: 24384256. 10: Limebeer CL, Abdullah RA, Rock EM, Imhof E, Wang K, Lichtman AH, Parker LA. Attenuation of anticipatory nausea in a rat model of contextually elicited conditioned gaping by enhancement of the endocannabinoid system. Psychopharmacology (Berl). 2014 Feb;231(3):603-12. doi: 10.1007/s00213-013-3282-7. Epub 2013 Sep 17. PubMed PMID: 24043345. 11: Wiskerke J, Irimia C, Cravatt BF, De Vries TJ, Schoffelmeer AN, Pattij T, Parsons LH. Characterization of the effects of reuptake and hydrolysis inhibition on interstitial endocannabinoid levels in the brain: an in vivo microdialysis study. ACS Chem Neurosci. 2012 May 16;3(5):407-17. doi: 10.1021/cn300036b. Epub 2012 Apr 22. PubMed PMID: 22860210; PubMed Central PMCID: PMC3382459. 12: Wise LE, Long KA, Abdullah RA, Long JZ, Cravatt BF, Lichtman AH. Dual fatty acid amide hydrolase and monoacylglycerol lipase blockade produces THC-like Morris water maze deficits in mice. ACS Chem Neurosci. 2012 May 16;3(5):369-78. doi: 10.1021/cn200130s. Epub 2012 Jan 27. PubMed PMID: 22860205; PubMed Central PMCID: PMC3382457. 13: Long JZ, Nomura DK, Vann RE, Walentiny DM, Booker L, Jin X, Burston JJ, Sim-Selley LJ, Lichtman AH, Wiley JL, Cravatt BF. Dual blockade of FAAH and MAGL identifies behavioral processes regulated by endocannabinoid crosstalk in vivo. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20270-5. doi: 10.1073/pnas.0909411106. Epub 2009 Nov 16. PubMed PMID: 19918051; PubMed Central PMCID: PMC2787168.