KML 29 |
| Catalog No.GC17385 |
KML 29 is reported to display IC50 values of 43, 15, and 5.9 nM toward rat, mouse, and human monoacylglycerol lipase (MAGL), respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1380424-42-9
Sample solution is provided at 25 µL, 10mM.
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KML 29 is reported to display IC50 values of 43, 15, and 5.9 nM toward rat, mouse, and human monoacylglycerol lipase (MAGL), respectively [1]. KML29 potently and selectively inhibited MAGL in vitro and in vivo with minimal cross-reactivity toward other central and peripheral serine hydrolases, including no detectable activity against FAAH [1].
KML 29 acted as a selective MAGL inhibitor showed antiproliferative activity against B16-F10 and HT-29 cells, while showed no significant effect on A431, H1975, OVCAR-3, HCC827, Hela and A549 cell lines [2].
KML 29 delays onset, progression and survival in the low-copy SOD1G93A Amyotrophic lateral sclerosis (ALS) mouse. oral administration of KML 29 is therapeutic by delaying onset, improving symptoms and extending lifespan, which was associated with increasing tissue levels of neurotrophic factors and decreasing pro-inflammatory cytokines [3]. Acute administration of KML 29 mostly increased 2-AG levels in fat, brain and spinal cord without any effect on AEA levels. KML 29 also reduced arachidonic acid levels in the CNS and peripheral organs [4].
References:
[1]. J.W. Chang, M.J. Niphakis, K.M. Lum, A.B. Cognetta 3rd, C. Wang, M.L. Matthews, S. Niessen, M.W. Buczynski, L.H. Parsons, B.F. Cravatt. Highly selective inhibitors of monoacylglycerol lipase bearing a reactive group that is bioisosteric with endocannabinoid substrates. Chem. Biol., 19 (2012), pp. 579-588
[2]. Deng H, Lei Q, Yang N, et al. Discover Monoacylglycerol Lipase Inhibitors by Combination of Fluorogenic Substrate Assay and Activity-Based Protein Profiling[J]. Frontiers in pharmacology, 2022: 3328.
[3]. N. Pasquarelli, M. Engelskirchen, J. Hanselmann, S. Endres, C. Porazik, H. Bayer, E. Buck, M. Karsak, P. Weydt, B. Ferger, A. Witting. Evaluation of monoacylglycerol lipase as a therapeutic target in a transgenic mouse model of ALS. Neuropharmacology, 124 (2017), pp. 157-169
[4]. N Pasquarelli, et al., Comparative biochemical characterization of the monoacylglycerol lipase inhibitor KML29 in brain, spinal cord, liver, spleen, fat and muscle tissue. Neuropharmacology 91, 148-156 (2015).
| Cell experiment [1]: | |
Cell lines | A431, H1975, B16-F10, OVCAR-3, HT-29, HCC827, Hela, A549 |
Preparation Method | cells (~1,000 per well) in 100 µl of culture medium were plated in a 96-well plate for 24 h and 100 µl of medium with KML29 was added to each well for 48 h. Then 10 µl of CCK8 solution was added and incubated at 37℃ for 2 h. |
Reaction Conditions | 20 µM KML29 for 48 h |
Applications | The selective MAGL inhibitor KML29 showed antiproliferative activity against B16-F10 and HT-29 cells. |
| Animal experiment [2]: | |
Animal models | MCAO rats |
Preparation Method | 1 mg/kg KML 29, a potent covalent inhibitor of MAGL, was administered intravenously for three days. |
Dosage form | intravenous injection, 1 mg/kg/d for 3 days |
Applications | Treatment with KML 29 reduced the area showing lower radioactivity in the ipsilateral region. In the ipsilateral side of the ischemia rat with no medication, the AUC ratios in the cortex and striatum were 0.49 ± 0.04 and 0.73 ± 0.02, respectively. The corresponding ratios were improved 0.72 ± 0.07 in the cortex and 0.88 ± 0.04 in the striatum by KML 29 treatment, respectively. |
References: | |
| Cas No. | 1380424-42-9 | SDF | |
| Chemical Name | 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(bis(benzo[d][1,3]dioxol-5-yl)(hydroxy)methyl)piperidine-1-carboxylate | ||
| Canonical SMILES | FC(F)(F)C(OC(N1CCC(C(C2=CC3=C(OCO3)C=C2)(O)C4=CC5=C(OCO5)C=C4)CC1)=O)C(F)(F)F | ||
| Formula | C24H21F6NO7 | M.Wt | 549.42 |
| Solubility | DMSO: 2 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8201 mL | 9.1005 mL | 18.201 mL |
| 5 mM | 0.364 mL | 1.8201 mL | 3.6402 mL |
| 10 mM | 0.182 mL | 0.9101 mL | 1.8201 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)
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