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Purity: ≥98%
| Targets |
PF-06471553 targets monoacylglycerol acyltransferase 3 (MGAT3), an enzyme involved in the synthesis of triacylglycerols (TAGs). MGAT3 catalyzes the acylation of monoacylglycerol to diacylglycerol, a key step in the monoacylglycerol pathway of TAG synthesis. This pathway is particularly important in the intestine for the absorption and re-esterification of dietary fats. PF-06471553 selectively inhibits MGAT3 with high in vitro potency and cell efficacy. The compound's selectivity for MGAT3 over other acyltransferases (DGAT1, DGAT2, MGAT1, MGAT2) makes it a valuable tool for studying the specific role of MGAT3 in lipid metabolism.
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| ln Vitro |
With an IC50 of 92 nM, PF-06471553 (6f) is a strong and selective inhibitor of monoacylglycerol acyltransferase 3 (MGAT3) that exhibits selectivity for MGAT3 over DGAT1 (IC50, >50 μM) and DGAT2 (IC50, >50 μM) by more than 160 times in vitro. MGAT1 (IC50, 14.9 μM), MGAT2 (IC50, 19.8 μM), and >100 μM. With an IC50 of 205 nM (pIC50, 6.69), PF-06471553 demonstrates inhibitory efficacy against MGAT3 in HEK-293 cells[1].
PF-06471553 demonstrates potent in vitro activity against MGAT3 with an IC50 of 92 nM. In HEK-293 cells, the compound inhibits MGAT3 activity with an IC50 of 205 nM (pIC50 = 6.69). PF-06471553 displays >160-fold in vitro selectivity for MGAT3 over DGAT1 (IC50 >50 μM), DGAT2 (IC50 >100 μM), MGAT1 (IC50 = 14.9 μM), and MGAT2 (IC50 = 19.8 μM). This high selectivity minimizes off-target effects and allows for the specific interrogation of MGAT3-dependent lipid metabolic pathways. The compound's cell efficacy has been demonstrated in HEK-293 cell-based assays. |
| ln Vivo |
In addition to DGAT1 and DGAT2 inhibitors, PF-06471553 (200 mg/kg, oral) demonstrated significant inhibitory effects on glycerol-d5 incorporation into triolein in hMGAT3 mice, while having no effect on WT mice [1].
In vivo, PF-06471553 has been evaluated in hMGAT3 transgenic mice. At an oral dose of 200 mg/kg (p.o.), PF-06471553, in addition to DGAT1 and DGAT2 inhibitors, displays additional inhibition of glycerol-d5 incorporated triolein. The compound has no effect on wild-type (WT) mice, confirming its target specificity for MGAT3. PF-06471553 displayed suitable pharmacokinetic properties in mouse and demonstrated in vivo MGAT3 inhibition in a transgenic mouse model. These findings support the utility of PF-06471553 for studying the role of MGAT3 in lipid absorption and metabolism in vivo. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for PF-06471553 measures the inhibition of MGAT3 enzymatic activity. Recombinant human MGAT3 enzyme is incubated with varying concentrations of PF-06471553 (typically ranging from nanomolar to micromolar) in the presence of a monoacylglycerol substrate and acyl-CoA donor. The enzymatic reaction is monitored by measuring the production of diacylglycerol using chromatographic (LC-MS) or radiometric methods. The IC50 value of 92 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 DGAT1, DGAT2, MGAT1, and MGAT2. 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-06471553 is performed using HEK-293 cells engineered to express MGAT3. Cells are cultured in appropriate medium and treated with varying concentrations of PF-06471553 or vehicle control (DMSO) for specified time points. MGAT3 activity in cell lysates is measured by incubating with a monoacylglycerol substrate and acyl-CoA donor, and the production of diacylglycerol is quantified. The inhibition of MGAT3 activity is assessed, and IC50 values (205 nM, pIC50 = 6.69) are determined by fitting dose-response curves. The compound's effects on cellular lipid metabolism can also be assessed by measuring TAG synthesis and lipid accumulation.
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| Animal Protocol |
In vivo animal experiments with PF-06471553 are conducted using hMGAT3 transgenic mice and wild-type mice as controls. PF-06471553 is administered orally at a dose of 200 mg/kg. To assess MGAT3 inhibition in vivo, animals are dosed with glycerol-d5 (a stable isotope tracer) to label newly synthesized TAGs. The incorporation of glycerol-d5 into triolein (a TAG species) is measured by LC-MS. PF-06471553, in combination with DGAT1 and DGAT2 inhibitors, displays additional inhibition of glycerol-d5 incorporated triolein in hMGAT3 mice, while having no effect on WT mice. Body weight and general health status are monitored throughout the study to assess tolerability.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for PF-06471553 are partially documented. The compound has a molecular weight of 467.54 and a chemical formula of C23H25N5O4S. PF-06471553 is soluble in DMSO at 150 mg/mL (320.83 mM). The compound should be stored as a powder at -20°C for up to 3 years or in solvent at -80°C for up to 1 year. PF-06471553 displayed suitable PK properties in mouse. For in vivo administration, the compound is typically formulated using appropriate vehicles to ensure adequate solubility and stability. 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.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for PF-06471553 are not extensively documented in publicly available sources. As a research-grade compound, PF-06471553 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 |
Inhibitor of monoacylglycerol acyltransferase 3; structure described in the first article.
PF-06471553 is a research compound developed for studying the role of MGAT3 in lipid metabolism, particularly in intestinal fat absorption and triacylglycerol synthesis. The compound's high selectivity for MGAT3 over DGAT1, DGAT2, MGAT1, and MGAT2 (>160-fold) makes it a valuable tool for dissecting MGAT3-specific functions in lipid metabolic pathways. PF-06471553 has demonstrated in vivo efficacy in a transgenic mouse model, confirming its utility for studying MGAT3 biology. The compound is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical metabolic research. PF-06471553 is available from various chemical suppliers for research purposes. Its utility lies in its ability to selectively inhibit MGAT3 and probe its role in lipid absorption and metabolism. |
| Molecular Formula |
C23H25N5O4S
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| Molecular Weight |
467.54070353508
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| Exact Mass |
467.162
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| CAS # |
1808094-07-6
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| PubChem CID |
122189255
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| Appearance |
White to off-white solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
801
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C=CC2CN(C(CC3C=CC=C(C=3)OC)=O)CC=2C=1)(NC1C=NN(C2CCC2)N=1)(=O)=O
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| InChi Key |
GRXCLNMCJWKTAT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H25N5O4S/c1-32-20-7-2-4-16(10-20)11-23(29)27-14-17-8-9-21(12-18(17)15-27)33(30,31)26-22-13-24-28(25-22)19-5-3-6-19/h2,4,7-10,12-13,19H,3,5-6,11,14-15H2,1H3,(H,25,26)
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| Chemical Name |
N-(2-cyclobutyl-2H-1,2,3-triazol-4-yl)-2-(2-(3-methoxyphenyl)acetyl)isoindoline-5-sulfonamide
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| Synonyms |
PF-06471553; PF-6471553; PF 06471553; PF 6471553; PF06471553; PF6471553.
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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 : ≥ 150 mg/mL (~320.83 mM)
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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 | 2.1389 mL | 10.6943 mL | 21.3885 mL | |
| 5 mM | 0.4278 mL | 2.1389 mL | 4.2777 mL | |
| 10 mM | 0.2139 mL | 1.0694 mL | 2.1389 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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