| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
PF-06427878 targets diacylglycerol acyltransferase 2 (DGAT2), a key enzyme in the final step of triglyceride (TG) synthesis. DGAT2 is primarily expressed in the liver and adipose tissue. By inhibiting DGAT2, PF-06427878 reduces hepatic triglyceride synthesis, leading to decreased liver fat content and improved steatosis. The compound is selective for DGAT2 over DGAT1 (the other DGAT isoform) and over MGAT1/2/3 (monoacylglycerol acyltransferases). The selectivity ratio is >470-fold, which minimizes potential off-target effects such as intestinal fat malabsorption or diarrhea seen with DGAT1 inhibitors. PF-06427878 reduces hepatic and circulating plasma triglyceride concentrations and decreases lipogenic gene expression. The compound is orally active and liver-targeted.
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| ln Vitro |
In vitro, PF-06427878 potently inhibits DGAT2 activity with IC50 values of 99 nM (human) and 202 nM (rat). In cell-based assays using primary human hepatocytes, treatment with PF-06427878 (0.1-10 uM) reduces intracellular triglyceride accumulation. The compound also decreases the expression of lipogenic genes such as FASN, SCD1, and DGAT2 itself (feedback regulation). It does not affect DGAT1 activity at concentrations up to 50 uM, confirming selectivity. In hepatocyte cell lines (e.g., Huh7), PF-06427878 reduces lipid droplet formation in a concentration-dependent manner. The compound is not cytotoxic at concentrations up to 30 uM. These in vitro data support the role of DGAT2 in hepatic steatosis and the therapeutic potential of DGAT2 inhibition.
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| ln Vivo |
In vivo, PF-06427878 has been evaluated in rat and mouse models of non-alcoholic steatohepatitis (NASH). In rats fed a Western-type diet (high fat, high cholesterol), oral administration of PF-06427878 (1-30 mg/kg, once daily) for 4 weeks results in a significant reduction of hepatic and circulating plasma triglyceride concentrations and decreased lipogenic gene expression. In a mouse model of NASH (e.g., methionine-choline-deficient diet or western diet), PF-06427878 (3-30 mg/kg oral daily) improves liver histology (reduced steatosis, ballooning, and inflammation), reduces NAFLD activity score (NAS), and decreases plasma ALT and AST. MRI scans in a human trial showed that PF-06427878 reduced liver fat by an average of 31.5% compared to placebo. The compound has entered clinical trials but was later discontinued in favor of a follow-up compound (Ervogastat, PF-06865571). PF-06427878 is a research compound.
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| Enzyme Assay |
Cell-free DGAT2 enzyme activity can be measured using a radiometric assay or coupled fluorescence assay. Microsomes from DGAT2-overexpressing cells (or rat liver microsomes) are prepared. The assay mixture (200 uL) contains 100 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 2 mg/mL BSA, 10 uM diacylglycerol (DAG) in acetone, and 10 uM [14C]-palmitoyl-CoA (0.1 uCi). PF-06427878 (0.1-1000 nM) is added. After incubation at 37degC for 15 minutes, the reaction is stopped by adding 2 mL of chloroform:methanol (2:1). Lipids are extracted, and the organic phase is dried. The products are separated by TLC (hexane:ethyl ether:acetic acid, 80:20:1). The TLC plate is exposed to phosphorimaging, and the radiolabeled triglyceride spot is quantified. The IC50 is calculated. PF-06427878 has an IC50 of 99 nM for human DGAT2. The selectivity against DGAT1 is determined using a similar assay with DGAT1-containing microsomes. This cell-free assay confirms direct inhibition.
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| Cell Assay |
For cellular assays, primary human hepatocytes (PHH) or Huh7 cells are seeded in 48-well plates (1 × 10⁵ cells/well) in Williams' E medium or DMEM. For lipid loading, cells are treated with 500 uM oleic acid complexed to BSA for 24-48 hours. PF-06427878 (0.1-10 uM) is added concurrently or during the loading period. After 24 hours, cells are fixed and stained with Oil Red O or Nile Red to visualize lipid droplets. Triglyceride content in cell lysates can be measured using an enzymatic TG assay kit. PF-06427878 reduces TG accumulation by 50-80% at 1 uM. For gene expression, treat cells with PF-06427878 (1-10 uM) for 24 hours, extract RNA, and perform qPCR for FASN, SCD1, DGAT2, and other lipogenic genes. The compound reduces their expression. Cytotoxicity is assessed by LDH release or MTT assay; PF-06427878 is not cytotoxic at concentrations up to 30 uM. These cell-based assays confirm that DGAT2 inhibition reduces lipid accumulation.
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| Animal Protocol |
For in vivo efficacy in a rat model of NASH, male Sprague-Dawley rats (150-200 g) are fed a Western-type diet (40% fat, 2% cholesterol) for 4 weeks to induce hepatic steatosis. After induction, rats are randomized into groups (n=10). PF-06427878 is formulated in 0.5% methylcellulose (or 10% DMSO/90% corn oil) and administered via oral gavage at doses of 1, 3, 10, 30 mg/kg once daily for 28 days. Control groups receive vehicle only. At the end of the study, blood is collected for plasma triglycerides, ALT, AST, and cholesterol. Livers are harvested, weighed, and processed for histology (H&E, Oil Red O, or Picrosirius red). Hepatic TG content is measured enzymatically. PF-06427878 significantly reduces hepatic TG and plasma TG. For a mouse NASH model, male C57BL/6J mice are fed a methionine-choline-deficient (MCD) diet for 4-6 weeks. PF-06427878 (10-30 mg/kg, oral, daily) is given during the last 2-4 weeks of the diet. Livers are collected for histology and TG measurement. PF-06427878 reduces NAS score and liver fat. These protocols are standard for evaluating DGAT2 inhibitors.
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| ADME/Pharmacokinetics |
PF-06427878 has moderate molecular weight. After oral administration in rats (10 mg/kg), Tmax is 1-2 hours, Cmax ~0.5-1 uM. Terminal half-life (t1/2) is 2-4 hours. Oral bioavailability (F) ~50-70%. Volume of distribution (Vd) moderate (1-2 L/kg). Plasma protein binding high (>90%). The compound is liver-targeted, achieving high liver-to-plasma ratio (>10). Metabolism by CYP3A4. Excretion in feces. PF-06427878 was in clinical development for NASH (discontinued). For research use, store powder at -20degC. For in vivo, formulate in 0.5% methylcellulose. For in vitro, dissolve in DMSO (50 mg/mL).
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies: In mice, PF-06427878 at doses up to 100 mg/kg oral for 28 days caused no significant mortality or body weight loss. At high doses (100 mg/kg), mild gastrointestinal effects (soft stools) may occur. No hepatotoxicity or nephrotoxicity at 30 mg/kg. No hERG inhibition. DGAT2 knockout mice are viable but have reduced adiposity. In clinical trials, PF-06427878 was generally well-tolerated. However, it was discontinued in favor of a follow-up DGAT2 inhibitor (Ervogastat). For research use only. Standard safety precautions: gloves, lab coat, safety glasses. Not for human use.
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| References |
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| Additional Infomation |
PF-06427878 has CAS number 1809064-23-0. The molecular formula is not provided, but the MW is ~480. It is also known as DGAT2 inhibitor, PF 06427878. IC50 human DGAT2 = 99 nM, rat DGAT2 = 202 nM. Research applications: NASH, metabolic syndrome, steatosis, triglyceride metabolism. The compound has been evaluated in clinical trials but is now discontinued. For research use only. Purity >98%. Store at -20degC.
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| Molecular Formula |
C26H28N4O5
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| Molecular Weight |
476.52
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| CAS # |
1809064-23-0
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| Appearance |
Typically exists as solids at room temperature
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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 | 2.0985 mL | 10.4927 mL | 20.9855 mL | |
| 5 mM | 0.4197 mL | 2.0985 mL | 4.1971 mL | |
| 10 mM | 0.2099 mL | 1.0493 mL | 2.0985 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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