[CAS NO. 1380424-42-9] KML29
PRODUCTS SPECIFICATIONS [1380424-42-9]
DESCRIPTION [1380424-42-9]
Overview
| MDL | MFCD22987957 |
|---|---|
| Molecular Weight | 549.42 |
| Molecular Formula | C24H21F6NO7 |
| SMILES | O=C(N1CCC(C(C2=CC=C(OCO3)C3=C2)(C4=CC=C(OCO5)C5=C4)O)CC1)OC(C(F)(F)F)C(F)(F)F |
2 Publications Citing Use of MCE
Summary
KML29 is an extremely selective, orally active and irreversible MAGL inhibitor, with IC 50 values of 15 nM, 43 nM and 5.9 nM for mouse, rat and human MAGL , respectively. KML29 exhibits minimal cross-reactivity toward other central and peripheral serine hydrolases , including no detectable activity against FAAH [1] [2] .
IC50 & Target
IC50: 15 nM (mouse MAGL), 43 nM (rat MAGL), 5.9 nM (human MAGL) [2] .
In Vitro
KML29 dose-dependently elevates brain 2-AG level up to 10-fold without alteration in brain levels of anandamide, palmitoylethanolamide, and oleoylethanolamide
[2]
.
KML29 is a potent inhibitor of 2-AG hydrolysis, but did not affect AEA hydrolysis at any concentration tested
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 50 mg/mL ( 91.01 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8201 mL | 9.1005 mL | 18.2010 mL |
| 5 mM | 0.3640 mL | 1.8201 mL | 3.6402 mL |
| 10 mM | 0.1820 mL | 0.9101 mL | 1.8201 mL |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.55 mM); Clear solution
References
- [1] Natsuo Ueda, et al. Discrimination between two endocannabinoids. Chem Biol. 2012 May 25;19(5):545-7.
- [2] Jae Won Chang, et al. Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem Biol. 2012 May 25;19(5):579-88.
- [3] B M Ignatowska-Jankowska, et al. In vivo characterization of the highly selective monoacylglycerol lipase inhibitor KML29: antinociceptive activity without cannabimimetic side effects. Br J Pharmacol. 2014 Mar;171(6):1392-407.