| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Other Sizes |
Purity: ≥98%
| Targets |
KML-29 targets monoacylglycerol lipase (MAGL), a key enzyme in the endocannabinoid system that degrades 2-arachidonoylglycerol (2-AG). It exhibits potent inhibition of human, mouse, and rat MAGL with IC₅₀ values of 5.9, 15, and 43 nM, respectively. KML-29 has minimal cross-reaction with other serine hydrolases, including FAAH. By inhibiting MAGL, KML-29 increases 2-AG levels, modulating endocannabinoid signaling. Its selectivity makes it a valuable tool for studying MAGL function.
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| ln Vitro |
KML29 dose-dependently raises brain 2-AG levels up to ten times without changing anandamide, palmitoylethanolamide, or oleoylethanolamide levels in the brain [2]. KML29 is a strong inhibitor of the hydrolysis of 2-AG, whereas it has no effect on the hydrolysis of AEA at any tested concentration [2].
In vitro, KML-29 is a highly selective and potent MAGL inhibitor. It exhibits IC₅₀ values of 5.9, 15, and 43 nM for human, mouse, and rat MAGL, respectively. It has minimal cross-reaction with other central and peripheral serine hydrolases including FAAH. In cell-based assays, KML-29 treatment results in increased 2-AG levels and modulation of endocannabinoid signaling. The compound's effects on MAGL activity are assessed using enzyme activity assays. |
| ln Vivo |
KML29 prevents the analgesic effect without causing adverse effects similar to cannabis [3]. The preventive effect of KML29 (20 mg/kg) against fever produced by LPS is considerable but moderate [3].
In vivo, KML-29 with gabapentin synergistically produces analgesia in mice. As a MAGL inhibitor, it modulates endocannabinoid signaling and has been shown to have effects against neuropathic pain. KML-29 is primarily applied in preclinical models to explore therapeutic strategies targeting the endocannabinoid system. The compound's effects on pain, inflammation, and metabolism are being studied. Comprehensive in vivo studies are ongoing. |
| Enzyme Assay |
In vitro enzyme assays for KML-29 involve measuring its inhibition of MAGL activity. The enzyme is incubated with varying concentrations of KML-29 in the presence of a fluorogenic substrate. The cleavage of the substrate is measured fluorometrically, and the IC₅₀ is calculated. Selectivity profiling is conducted using similar assays with other serine hydrolases, including FAAH. These assays confirm the compound's potent and selective MAGL inhibition.
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| Cell Assay |
In vitro cell-based assays for KML-29 evaluate its effects on endocannabinoid signaling. Cells are cultured and treated with KML-29, and 2-AG levels are measured by LC-MS/MS. The compound's effects on downstream signaling pathways, such as CB1 receptor activation, are assessed. These assays confirm the compound's functional activity as a MAGL inhibitor.
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| Animal Protocol |
Animal/Disease Models: C57Bl/6 mice[2].
Doses: 1-40 mg/kg. Route of Administration: PO single dose. Experimental Results: Selective inhibition of MAGL in mice. Animal/Disease Models: Wistar albino male rat [2]. Doses: 20 mg/kg (+LPS E. coli O111:B4 (250 µg/kg, SC)). Management: SC. Experimental Results: Simultaneous administration of KML29 and LPS E. coli O111:B4 Dramatically diminished ΔT (Type 1 error 5%, 1.7-fold) compared to saline + LPS E. coli O111:B4. Coadministration of KML29 with LPS E. coli O111:B4 resulted in a reduction in the fever plateau compared with administration of LPS EE E. coli O111:B4 + saline. In vivo animal experiments for KML-29 have been conducted in models of neuropathic pain. Mice are treated with KML-29, and pain responses are assessed using behavioral tests such as the von Frey test or hot plate test. KML-29 with gabapentin synergistically produces analgesia in mice. The compound's effects on pain, inflammation, and metabolic parameters are assessed. Pharmacokinetic studies are conducted to determine the compound's half-life, clearance, and tissue distribution. Comprehensive in vivo studies are ongoing. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for KML-29 are limited. The compound has a molecular weight of 549.42 g/mol and a molecular formula of C₂₄H₂₁F₆NO₇. It is stored at -20°C. The compound's metabolic stability, half-life, and bioavailability have not been fully characterized. Comprehensive ADME studies are needed.
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| Toxicity/Toxicokinetics |
The toxicity profile of KML-29 has not been extensively characterized. As a research compound, it should be handled with appropriate safety precautions. The compound is for research use only and is not intended for human or veterinary use. Comprehensive toxicological studies are needed to fully characterize the safety profile of KML-29.
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| References | |
| Additional Infomation |
KML-29 is a highly selective and potent monoacylglycerol lipase (MAGL) inhibitor. It inhibits human, mouse, and rat MAGL with IC₅₀ values of 5.9, 15, and 43 nM, respectively. It has minimal cross-reaction with other serine hydrolases including FAAH. KML-29 is used as a pharmacological tool in neuroscience and immunology research. It is a research compound and has not progressed to clinical trials.
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| Molecular Formula |
C24H21F6NO7
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| Molecular Weight |
549.4224
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| Exact Mass |
549.122
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| CAS # |
1380424-42-9
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| Related CAS # |
1380424-42-9
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| PubChem CID |
71656212
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
554.8±50.0 °C at 760 mmHg
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| Flash Point |
289.3±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.544
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| LogP |
6.05
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
38
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| Complexity |
803
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
SXHQLPHDBLTFPM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H21F6NO7/c25-23(26,27)20(24(28,29)30)38-21(32)31-7-5-13(6-8-31)22(33,14-1-3-16-18(9-14)36-11-34-16)15-2-4-17-19(10-15)37-12-35-17/h1-4,9-10,13,20,33H,5-8,11-12H2 SMILES
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| 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
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| Synonyms |
KML-29 KML29 KML 29.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~91.01 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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