WWL70 | CAS#947669-91-2 | ABHD6 Inhibitor

MedKoo Cat#: 510348 | Name: WWL70

Description:

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

WWL70 is a potent inhibitor of α/β-hydrolase domain 6 (ABHD6) (IC50 = 70 nM), an enzyme which catalyzes the hydrolysis of 2-arachidonylglycerol.

Chemical Structure

WWL70

CAS#947669-91-2

Theoretical Analysis

MedKoo Cat#: 510348

Name: WWL70

CAS#: 947669-91-2

Chemical Formula: C27H23N3O3

Exact Mass: 437.1739

Molecular Weight: 437.50

Elemental Analysis: C, 74.13; H, 5.30; N, 9.60; O, 10.97

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
1g	USD 4,250.00	Ready to ship
2g	USD 6,450.00	Ready to ship

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Related CAS #

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Synonym

WWL 70; WWL70; WWL-70.

IUPAC/Chemical Name

4'-carbamoyl-[1,1'-biphenyl]-4-yl methyl(3-(pyridin-4-yl)benzyl)carbamate

InChi Key

QTWNORFUQILKJL-UHFFFAOYSA-N

InChi Code

InChI=1S/C27H23N3O3/c1-30(18-19-3-2-4-24(17-19)22-13-15-29-16-14-22)27(32)33-25-11-9-21(10-12-25)20-5-7-23(8-6-20)26(28)31/h2-17H,18H2,1H3,(H2,28,31)

SMILES Code

CN(C(OC1=CC=C(C2=CC=C(C(N)=O)C=C2)C=C1)=O)CC3=CC=CC(C4=CC=NC=C4)=C3

Appearance

White to off-white 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

Certificate of Analysis

View CoA: current batch, Lot#S7S11C27

View CoA: current batch, Lot#S9S04C23

QC Data

View QC data: current batch, Lot#S7S11C27

View QC data: current batch, Lot#S9S04C23

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

WWL70 is a selective alpha/beta hydrolase domain 6 (ABHD6) inhibitor with an IC50 of 70 nM.

In vitro activity:

In this study, WWL70 treatment inhibited 2-AG hydrolysis and increased the intracellular levels of 2-AG. WWL70 also significantly reduced the production of PGE2 in LPS-activated BV2 and primary microglia cells. However, the increased PGE2 production was not affected by another newly developed ABHD6 inhibitor KT182, and the inhibitory effect of WWL70 was also observed in BV2 cells with ABHD6 knockdown. These results suggest that the inhibitory effect of WWL70 on PGE2 production in LPS-activated microglia is not dependent on its inhibition of ABHD6 activity. Treatment with WWL70 reduced the expression of both COX2 and mPGES, the metabolic enzymes crucial for PGE2 production from AA. Furthermore, WWL70 directly inhibited the enzymatic activity of microsomal PGE2 biosynthesis. Reference: J Neuroinflammation. 2017; 14: 7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234251/

In vivo activity:

The increased activation of microglia and astrocytes in the DRG, sciatic nerve, and dorsal horn of the lumbar spinal cord of the CCI (chronic constriction injury) vehicle group indicates the importance of glial activation in CCI-induced neuropathic pain. Considering the inhibitory effect of WWL70 on microglial activation in previous studies, the possibility of WWL70 in the treatment of neuropathic pain was explored. As anticipated, systemic administration of WWL70 to mice with CCI dramatically reduced microglia and astrocyte activation in the spinal cord dorsal horn and macrophage infiltration in the sciatic nerve and DRG. Moreover, the reduced activation of glial cells by WWL70 treatment after CCI further alleviated the release of pro-nociceptive mediators to facilitate pain relief. These results are consistent with several recent studies indicating spinal microgliosis and macrophage accumulation in DRG and sciatic nerve contribute to pain hypersensitivity after peripheral nerve injury. Reference: J Neuroinflammation. 2018; 15: 9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759843/

	Solvent	mg/mL	mM
Solubility
	DMSO	7.6	17.30
	DMF	2.0	4.57
	DMF:PBS (pH 7.2) (1:3)	0.2	0.46

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 437.50 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. Tanaka M, Moran S, Wen J, Affram K, Chen T, Symes AJ, Zhang Y. WWL70 attenuates PGE2 production derived from 2-arachidonoylglycerol in microglia by ABHD6-independent mechanism. J Neuroinflammation. 2017 Jan 10;14(1):7. doi: 10.1186/s12974-016-0783-4. PMID: 28086912; PMCID: PMC5234251. 2. Wen J, Jones M, Tanaka M, Selvaraj P, Symes AJ, Cox B, Zhang Y. WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms. J Neuroinflammation. 2018 Jan 8;15(1):9. doi: 10.1186/s12974-017-1045-9. PMID: 29310667; PMCID: PMC5759843. 3. Tchantchou F, Zhang Y. Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury. J Neurotrauma. 2013 Apr 1;30(7):565-79. doi: 10.1089/neu.2012.2647. Epub 2013 Apr 5. PMID: 23151067; PMCID: PMC3636589.

In vitro protocol:

In vivo protocol:

1. Wen J, Jones M, Tanaka M, Selvaraj P, Symes AJ, Cox B, Zhang Y. WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms. J Neuroinflammation. 2018 Jan 8;15(1):9. doi: 10.1186/s12974-017-1045-9. PMID: 29310667; PMCID: PMC5759843. 2. Tchantchou F, Zhang Y. Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury. J Neurotrauma. 2013 Apr 1;30(7):565-79. doi: 10.1089/neu.2012.2647. Epub 2013 Apr 5. PMID: 23151067; PMCID: PMC3636589.

1: Alhouayek M, Masquelier J, Cani PD, Lambert DM, Muccioli GG. Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17558-63. doi: 10.1073/pnas.1314017110. Epub 2013 Oct 7. PubMed PMID: 24101490; PubMed Central PMCID: PMC3808642. 2: Tchantchou F, Zhang Y. Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury. J Neurotrauma. 2013 Apr 1;30(7):565-79. doi: 10.1089/neu.2012.2647. Epub 2013 Apr 5. PubMed PMID: 23151067; PubMed Central PMCID: PMC3636589. 3: Straiker A, Hu SS, Long JZ, Arnold A, Wager-Miller J, Cravatt BF, Mackie K. Monoacylglycerol lipase limits the duration of endocannabinoid-mediated depolarization-induced suppression of excitation in autaptic hippocampal neurons. Mol Pharmacol. 2009 Dec;76(6):1220-7. doi: 10.1124/mol.109.059030. Epub 2009 Sep 18. PubMed PMID: 19767452; PubMed Central PMCID: PMC2784730.