| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
IC50: 14 nM (DGAT2)[1]
PF-06424439 targets diacylglycerol acyltransferase 2 (DGAT2), an enzyme that catalyzes the final step in triglyceride synthesis. It inhibits DGAT2 with an IC50 of 14 nM. The compound interacts with DGAT2 in a noncompetitive manner with respect to the acyl-CoA substrate and is a slowly reversible, time-dependent inhibitor. It is selective for DGAT-2 over DGAT-1, MGAT-2, and MGAT-3 (IC50s >50 μM). |
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| ln Vitro |
In vitro, PF-06424439 demonstrates potent inhibition of DGAT2 with an IC50 of 14 nM. It shows selectivity for DGAT-2 over the related acyltransferases DGAT-1, MGAT-2, and MGAT-3, with IC50 values exceeding 50 μM. Inhibition of DGAT2 disrupts the final step in triglyceride synthesis, reducing triglyceride production in adipocytes.
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| ln Vivo |
Mice (Ldlr-/-) treated with PF-06424439 methanesulfonate (oral; 60 mg/kg/day; for 3 days) have lower plasma TG and cholesterol levels as well as lower circulating lipid levels [1]. Rats administered PF-06424439 methanesulfonate (iv; 1 mg/kg) intravenously show a short half-life, moderate steady-state volume of distribution (Vdss), and moderate clearance [1].
In vivo, PF-06424439 (0.1-10 mg/kg) reduces plasma triglyceride levels in sucrose-fed rats in a dose-dependent manner. At 60 mg/kg per day, it reduces plasma levels of cholesterol and triglycerides as well as hepatic triglycerides in LDL receptor knockout mice fed a high-fat, high-cholesterol diet. These effects support its potential for treating metabolic disorders. |
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for PF-06424439 involve DGAT2 enzyme activity assays. IC50 values are determined using purified DGAT2 enzyme and appropriate substrates. Selectivity is confirmed by testing against DGAT-1, MGAT-2, and MGAT-3. The compound's noncompetitive and time-dependent inhibition mechanism is characterized through kinetic analysis.
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| Cell Assay |
In vitro cell-based assays for PF-06424439 use epithelial colon cells and colorectal cancer stem cells to study its effects on cell mortality and lipid synthesis. Cells are treated with the compound, and triglyceride production, lipid accumulation, and cell viability are assessed. The compound's effects on DGAT2 activity are confirmed by measuring triglyceride levels in treated cells.
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| Animal Protocol |
Animal/Disease Models: Male low-density lipoprotein receptor (Ldlr) knockout mice (Ldlr-/-)[1]
Doses: 60 mg/kg Route of Administration: Po; daily; for 3 days Experimental Results: decreased plasma TG and cholesterol levels and diminished nonsignificant in circulating lipids. Animal/Disease Models: Male Wistar-Han rats[1] Doses: 1 mg/kg Route of Administration: Iv Experimental Results: demonstrated moderate clearance and a short half-life with t1/2=1.39 h. In vivo animal studies for PF-06424439 have been conducted in sucrose-fed rats and LDL receptor knockout mice. In rats, the compound (0.1-10 mg/kg) reduces plasma triglyceride levels in a dose-dependent manner. In LDL receptor knockout mice fed a high-fat, high-cholesterol diet, 60 mg/kg per day reduces plasma cholesterol and triglycerides as well as hepatic triglycerides. |
| ADME/Pharmacokinetics |
PF-06424439 Mesylate has a molecular weight of 536.04 g/mol. The compound is orally bioavailable. It has moderate clearance and a short half-life. Storage: dry, dark, at 0-4°C for short term or -20°C for long term. Purity is >98%. The compound is soluble in DMSO.
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| Toxicity/Toxicokinetics |
Specific toxicological data for PF-06424439 are not detailed in the available literature. The compound is classified for research use only and is not intended for human therapeutic applications. As a DGAT2 inhibitor that reduces triglyceride synthesis, potential toxicities would relate to effects on lipid metabolism and fat storage, though formal toxicological profiles are not reported.
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| References |
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| Additional Infomation |
PF-06424439 Mesylate (CAS 1469284-79-4) is an orally bioavailable, potent, and selective DGAT2 inhibitor with an IC50 of 14 nM. It is selective for DGAT-2 over DGAT-1, MGAT-2, and MGAT-3 (IC50s >50 μM). In vivo, it reduces plasma and hepatic triglycerides. The compound is used in metabolic disorder research. No clinical trial data are available.
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| Molecular Formula |
C23H30CLN7O4S
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|---|---|
| Molecular Weight |
536.0468
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| Exact Mass |
535.176
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| CAS # |
1469284-79-4
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| Related CAS # |
PF-06424439;1469284-78-3
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| PubChem CID |
89854212
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| Appearance |
White to yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
36
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| Complexity |
777
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C=NN(C=1)C1(C2=NC3=C(C=CC(=N3)N3CCC[C@@H](C(N4CCCC4)=O)C3)N2)CC1.S(C)(=O)(=O)O
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| InChi Key |
ZSTFDNQQOJUJFL-XFULWGLBSA-N
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| InChi Code |
InChI=1S/C22H26ClN7O.CH4O3S/c23-16-12-24-30(14-16)22(7-8-22)21-25-17-5-6-18(26-19(17)27-21)29-11-3-4-15(13-29)20(31)28-9-1-2-10-281-5(2,3)4/h5-6,12,14-15H,1-4,7-11,13H2,(H,25,26,27)1H3,(H,2,3,4)/t15-/m1./s1
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| Chemical Name |
[(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonate
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| Synonyms |
PF06424439 Mesylate PF 06424439 Mesylate PF-06424439 Mesylate
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~250 mg/mL (~466.37 mM)
H2O : ~50 mg/mL (~93.27 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.88 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 20.8 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: ≥ 2.08 mg/mL (3.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (93.27 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8655 mL | 9.3275 mL | 18.6550 mL | |
| 5 mM | 0.3731 mL | 1.8655 mL | 3.7310 mL | |
| 10 mM | 0.1865 mL | 0.9327 mL | 1.8655 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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