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| WWL 70α/β-hydrolase domain 6 inhibitor |
Sample solution is provided at 25 µL, 10mM.
Nature.2017 Jan 19;541(7637):417-420.
Nature.2018 Nov;563(7731):407-411.Nature.2018 Jun 13.Nature.2018 Jun 27.Nature.2018 Mar 29;555(7698):673-677.Nature.2017 Sep 7;549(7670):96-100.Nature.2016 Apr 21;532(7599):398-401.
Science.2016 Aug 5;353(6299)594-8Nat Nanotechnol.2017 Dec;12(12):1190-1198.Nature Biotechnology.2017 Jun;35(6):569-576Nat Med.2018 Sep 17.Cell.2018 Dec 21. pii: S0092-8674(18)31561-7.Cell.Available online 25 October 2018.Cell.2018 Sep 27. pii: S0092-8674(18)31183-8.Cell.2018 Jun 28;174(1):172-186.e21.Cell.2018 Feb 22;172(5):1007-1021.e17.Cell.2017 Nov 30;171(6):1284-1300.e21.Cell.2017 Aug 17. pii: S0092-8674(17)30869-3.Cell.2017 Jul 13;170(2):312-323Nat Med.2018 Jan 29.Nat Med.2017 Nov;23(11):1342-1351.Cell.2017 Apr 6;169(2):286-300.Cell.2015 Aug 27;162(5):987-1002.Cell.2015 Feb 12;160(4):729-44.Nature Medicine.2017 Apr;23(4):493-500.Cancer Cell.2018 May 14;33(5):905-921.e5.Cancer Cell.2018 Apr 9;33(4):752-769.e8.Cancer Cell.2018 Mar 12;33(3):401-416.e8.Cancer Cell.2017 Aug 14;32(2):253-267.e5.Nat Methods.2018 Jul;15(7):523-526.Cell Stem Cell.2018 May 3;22(5):769-778.e4.Cell Stem Cell.2017 Nov 20. pii: S1934-5909(17)30375-2.Quality Control & MSDS
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- Purity = 98.16%
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Chemical structure
| Cell experiment[1]: | |
Cell lines | HEK293 cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
Reaction Conditions | 10 μM, 10 min |
Applications | Depolarization-induced suppression of excitation (DSE) is a major form of cannabinoid-mediated short-term retrograde neuronal plasticity and is found in numerous brain regions. ABHD6 is not present presynaptically in autaptic neurons and the ABHD6 inhibitor, WWL70, has no effect on the autaptic DSE time course. |
| Animal experiment[1]: | |
Animal models | Male C57BL/6 mice, 25–30 g |
Dosage form | WWL70 (5 mg/kg or 10 mg/kg) dissolved in 1% DMSO in physiologic saline was injected intraperitoneally 30 min after TBI, and then once a day for ≥ 7 days depending on the experimental design. |
Applications | WWL70, a selective ABHD6 inhibitor, improved motor coordination and working memory performance. WWL70 treatment reduced lesion volume in the cortex and neurodegeneration in the dendate gyrus. It also suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression of arginase-1 in the ipsilateral cortex at 3 and 7 days post-TBI, suggesting microglia/macrophages shifted from M1 to M2 phenotypes after treatment. The blood-brain barrier dysfunction at 3 and 7 days post-TBI was dramatically reduced. Furthermore, the beneficial effects of WWL70 involved up-regulation and activation of cannabinoid type 1 and type 2 receptors and were attributable to the phosphorylation of the extracellular signal regulated kinase and the serine/threonine protein kinase AKT. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: 1. Straiker A1, Hu SS, Long JZ et al. 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. 2. Tchantchou F1, 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. | |
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| Cas No. | 947669-91-2 | SDF | Download SDF |
| Chemical Name | 4"-carbamoyl-[1,1"-biphenyl]-4-yl methyl(3-(pyridin-4-yl)benzyl)carbamate | ||
| Canonical SMILES | O=C(N(C)CC1=CC=CC(C2=CC=NC=C2)=C1)OC3=CC=C(C=C3)C4=CC=C(C(N)=O)C=C4 | ||
| Formula | C27H23N3O3 | M.Wt | 437.49 |
| Solubility | ≥14.45mg/mL in DMSO | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
WWL 70 is a potent inhibitor of α/β-hydrolase domain 6 (ABHD6) with IC50 value of 70 nM [1].
WWL 70 is an O-aryl group-modified derivative of carbamate 18 which is a lead inhibitor of ABHD6 screened out by a functional proteomic strategy. WWL 70 is about 5-fold more potent than carbamate 18. The improved potency makes no difference in selectivity of WWL 70 and carbamate 18 as measured by competitive ABPP with brain membrane proteome. WWL 70 was selective against ABHD6 over other 27 SH activities except for ABHD10 which showed a significant reduction in activity in WWL 70-treated proteomes. However, WWL 70 had no effect on recombinant ABHD10 at concentration of 100 μM, suggesting that ABHD10 was not a real target [1].
References:[1] Li W, Blankman J L, Cravatt B F. A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. Journal of the American Chemical Society, 2007, 129(31): 9594-9595.
