| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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Purity: ≥98%
| Targets |
PF-06795071 targets monoacylglycerol lipase (MAGL), the primary enzyme responsible for hydrolyzing the endocannabinoid 2-arachidonoylglycerol (2-AG) in the central nervous system. MAGL inhibition provides a potential treatment approach to neuroinflammation through modulation of both the endocannabinoid pathway and arachidonoyl signaling in the CNS. PF-06795071 is a covalent MAGL inhibitor featuring a novel trifluoromethyl glycol leaving group. The design strategy focused on identifying an optimized leaving group that delivers MAGL potency, serine hydrolase selectivity, and CNS exposure while simultaneously reducing log D, improving solubility, and minimizing chemical lability.
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| ln Vitro |
PF-06795071 exhibits remarkable selectivity towards FAAH, demonstrating an IC50 of 3.1 μM[1].
PF-06795071 demonstrates potent in vitro activity against MAGL with an IC50 of 3 nM. The compound shows excellent selectivity against FAAH with an IC50 of 3.1 μM, indicating minimal cross-reactivity with this related serine hydrolase. PF-06795071 has a log D of 3.8 and a Cb,u/Cp,u ratio of 1.4, indicating good brain penetration. The compound's covalent binding mechanism ensures sustained inhibition of MAGL. PF-06795071's selectivity profile makes it a valuable tool compound for dissecting MAGL-dependent lipid signaling and studying 2-AG metabolism. |
| ln Vivo |
PF-06795071 achieves excellent CNS exposure and extended 2-AG elevation effect in vivo. The compound decreases brain inflammatory markers in response to an inflammatory challenge. PF-06795071 has a Cb,u/Cp,u ratio of 1.4, indicating good brain penetration. The compound's ability to elevate 2-AG levels in the CNS and reduce neuroinflammation supports its utility for studying the therapeutic potential of MAGL inhibition in neuroinflammatory and neurological disorders. Detailed in vivo efficacy data, including specific dosing regimens and effects on inflammatory markers, are available in the primary literature.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for PF-06795071 measures the inhibition of MAGL enzymatic activity. Recombinant human MAGL enzyme is incubated with varying concentrations of PF-06795071 (typically ranging from nanomolar to micromolar) in the presence of a fluorescent or radiolabeled substrate (e.g., 2-AG analog). The enzymatic reaction is monitored by measuring the hydrolysis of the substrate. The IC50 value of 3 nM is determined by fitting dose-response curves to the inhibition data. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Selectivity is assessed by testing the compound against FAAH (IC50 = 3.1 μM) and other serine hydrolases. The covalent binding mechanism can be confirmed by pre-incubation studies or mass spectrometry. Appropriate positive controls and negative controls are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for PF-06795071 is performed using cells that express MAGL, such as neuronal cells or macrophages. Cells are cultured in appropriate medium and treated with varying concentrations of PF-06795071 or vehicle control (DMSO) for specified time points. Following treatment, cells are lysed and the levels of 2-AG and other endocannabinoids are measured by liquid chromatography-mass spectrometry (LC-MS). The elevation of 2-AG levels is quantified and compared to vehicle-treated controls to assess the efficacy of MAGL inhibition. The compound's effects on downstream signaling pathways (e.g., CB1/CB2 receptor signaling) and inflammatory markers can also be assessed. Dose-response relationships are established by analyzing 2-AG accumulation across different compound concentrations.
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| Animal Protocol |
In vivo animal experiments with PF-06795071 are conducted using rodent models of neuroinflammation or other neurological disorders. PF-06795071 is administered via oral gavage or intraperitoneal injection at various doses. Brain and plasma concentrations of the compound are measured to assess CNS exposure (Cb,u/Cp,u = 1.4). 2-AG levels in brain tissues are measured by LC-MS to confirm target engagement and extended 2-AG elevation. Inflammatory markers (e.g., cytokines, prostaglandins) are measured in brain tissues to assess the anti-inflammatory effects of MAGL inhibition. Behavioral tests may be performed to assess the compound's effects on pain, anxiety, or other neurological endpoints. Body weight and general health status are monitored throughout the study.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for PF-06795071 are partially documented. The compound has a molecular weight of 399.34 and a chemical formula of C18H17F4N3O3. PF-06795071 has a log D of 3.8 and a Cb,u/Cp,u ratio of 1.4, indicating good brain penetration. The compound is soluble in DMSO for formulation purposes. The compound should be stored as a powder at -20°C for up to 3 years. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning. PF-06795071 is considered to have excellent CNS exposure.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for PF-06795071 are not extensively documented in publicly available sources. As a research-grade compound, PF-06795071 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References | |
| Additional Infomation |
PF-06795071 is a research compound developed for studying the role of MAGL in endocannabinoid signaling and neuroinflammation. The compound's high potency (IC50 = 3 nM), selectivity over FAAH (IC50 = 3.1 μM), and excellent CNS exposure (Cb,u/Cp,u = 1.4) make it a valuable tool for dissecting MAGL-dependent lipid signaling and studying 2-AG metabolism. PF-06795071 features a novel trifluoromethyl glycol leaving group that improves physicochemical properties compared to earlier inhibitor series. The compound achieves extended 2-AG elevation in vivo and decreases brain inflammatory markers. PF-06795071 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical neuroscience research. PF-06795071 is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C18H17F4N3O3
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| Molecular Weight |
399.339498281479
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| Exact Mass |
399.12
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| CAS # |
2075629-81-9
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| PubChem CID |
126502731
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| Appearance |
White to off-white solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
573
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| Defined Atom Stereocenter Count |
3
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| SMILES |
FC([C@@H](CO)OC(N1C[C@@H]2C(C3C=CN(C4C=CC(=CC=4)F)N=3)[C@@H]2C1)=O)(F)F
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| InChi Key |
MEDCQBUTCWNKGW-CLWVCHIJSA-N
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| InChi Code |
InChI=1S/C18H17F4N3O3/c19-10-1-3-11(4-2-10)25-6-5-14(23-25)16-12-7-24(8-13(12)16)17(27)28-15(9-26)18(20,21)22/h1-6,12-13,15-16,26H,7-9H2/t12-,13+,15-,16+/m1/s1
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| Chemical Name |
(2R)-1,1,1-Trifluoro-3-hydroxypropan-2-yl (1R,5S,6r)-6-[1-(4-Fluorophenyl)-1H-pyrazol-3-yl]-3-azabicyclo[3.1.0]hexane-3-carboxylate
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| Synonyms |
PF-06795071; PF 06795071; PF06795071.
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5041 mL | 12.5207 mL | 25.0413 mL | |
| 5 mM | 0.5008 mL | 2.5041 mL | 5.0083 mL | |
| 10 mM | 0.2504 mL | 1.2521 mL | 2.5041 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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