| Identification | Back Directory | [Name]
KML-29 | [CAS]
1380424-42-9 | [Synonyms]
KML-29
CS-2396
KML29 (KML-29)
KML29;KML-29;KML 29
4-[Bis(1,3-benzodioxol-5-yl)hydroxymethyl]-1-piperidinecarboxylic acid 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ester
1-Piperidinecarboxylic acid, 4-[bis(1,3-benzodioxol-5-yl)hydroxymethyl]-, 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ester | [Molecular Formula]
C24H21F6NO7 | [MDL Number]
MFCD22987957 | [MOL File]
1380424-42-9.mol | [Molecular Weight]
549.42 |
| Chemical Properties | Back Directory | [Melting point ]
204-206°C | [Boiling point ]
554.8±50.0 °C(Predicted) | [density ]
1.511±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C Freezer | [solubility ]
Chloroform (Slightly, Heated, Sonicated), Methanol (Slightly, Heated) | [form ]
Solid | [pka]
13.32±0.29(Predicted) | [color ]
White to Off-White | [InChIKey]
SXHQLPHDBLTFPM-UHFFFAOYSA-N | [SMILES]
FC(F)(F)C(OC(=O)N1CCC(CC1)C(O)(c4cc5c(cc4)OCO5)c2cc3c(cc2)OCO3)C(F)(F)F |
| Hazard Information | Back Directory | [Description]
Endocannabinoids such as 2-arachidonoyl glycerol (2-AG) and arachidonoyl ethanolamide are biologically active lipids that are involved in a number of synaptic processes including activation of cannabinoid receptors. Monoacylglycerol lipase (MAGL) is a serine hydrolase responsible for the hydrolysis of 2-AG to arachidonic acid and glycerol, thus terminating its biological function. KML29 is an O-hexafluoroisopropyl carbamate analog of JZL 184 (Item No. 13158) that potently and selectively inhibits MAGL (IC50s = 15, 43, and 5.9 nM in mouse, rat, and human brain proteomes, respectively) over FAAH (IC50s >50 μM).1 At 5-20 mg/kg, KML29 dose-dependently blocks mouse brain MAGL activity in vivo, without any measurable effect on FAAH activity.1 As a second generation MAGL inhibitor, KML29 supersedes the low-level cross reactivity that JZL 184 displays for FAAH yet still maintains comparable potency to its parent compound. | [Uses]
KML-29 is an extremely specific monoacylglycerol lipase (MAGL) inhibitor. KML-2 should be useful to distinguish between actions of 2-arachidonoyl glycerol (an endogenous ligand of cannabinoid receptors that is deactivated by MAGL) and anandamide, another endocannabinoid. | [in vivo]
KML29 enhibits antinociceptive activity without cannabimimetic side effects[3].
KML29 (20 mg/kg) has a significant but modest protective effect against LPS-induced fever[3].
| Animal Model: | C57Bl/6 mice[2]. | | Dosage: | 1-40 mg/kg. | | Administration: | P.O. single dose. | | Result: | Selectively inhibited MAGL in mice. |
| Animal Model: | Wistar albino male rats[2]. | | Dosage: | 20 mg/kg (+LPS E. coli O111:B4 (250 μg/kg, sc)). | | Administration: | SC. | | Result: | Administration of KML29 simultaneously with LPS E. coli O111:B4 significantly decreased ?T (with 5% type 1 error, 1.7 fold) compared to saline+LPS E. coli O111:B4. Administration of KML29 simultaneously with LPS E. coli O111:B4 resulted in decreased plateau phase of fever compared to LPS E. E. coli O111:B4+saline administration. |
| [storage]
Store at -20°C | [References]
[1] JAE WON CHANG. Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates.[J]. Chemistry & biology, 2012: 579-588. DOI: 10.1016/j.chembiol.2012.03.009 |
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