| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
PF-06260933 is a highly selective small-molecule inhibitor of MAP4K4 (Mitogen-activated protein kinase kinase kinase 4) with IC50 values of 3.7 and 160 nM for cell-freel assay and cell assay, respectively. Additionally, with IC50 values of 8 and 13 nM, it inhibits MINK and TNIK. Fasting hyperglycemia in mice has been shown to be reduced by PF-06260933. Recent research on the serine/threonine protein kinase MAP4K4, which is found in adipose tissue, the pancreas, muscle, and macrophages, suggests that it may be a promising target for anti-diabetic medications. The evaluation of MAP4K4 as a potential new anti-diabetic target is being done with PF-6260933.
| Targets |
MAP4K4 (IC50 = 3.7 nM)
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| ln Vitro |
PF-6260933 demonstrates good physicochemical characteristics and a moderate HLM clearance[1].
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| ln Vivo |
PF-6260933 exhibits a plasma exposure after oral dosing (10 mg/kg) that provided free drug concentrations above the cell IC50 value for about 4-6 h after administration in a mouse model. For use as a tool in an in vivo diabetes model, PF-6260933's PK properties in mice are suitable[1].
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| Enzyme Assay |
Aortas were lysed in 1% NP-40, 50 mM Tris pH 7.4, 150 mM NaCl, 50 mM EDTA, and 1 × HALT protease and phosphatase inhibitors (Thermo Scientific). Immunoprecipitates were then made using Bethyl MAP4K4 antibodies (503 A; 1 μg) or regular rabbit IgG (Cell Signaling 2729; 1 μg). The immunoprecipitates were combined with 1 μg of myelin basic protein (MBP) and 10 μCi of [γ-32P]ATP, and then incubated for 30 min at 30 °C in kinase buffer (20 mM HEPES, 10 nM MgCl2, 1 mM dithiothreitol (DTT), and protease and phosphatase inhibitor cocktail. Samples were electrophoretically separated on a 12% SDS-polyacrylamide gel and then autoradiographically viewed.
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| Cell Assay |
In EGM2 media, HUVECs are kept alive at 5% CO2 and 37°C. To ascertain whether pharmacological inhibition of MAP4K4 alters MAPK signaling in response to TNF-α, HUVECs or peritoneal macrophages are treated in vitro with vehicle or PF-06260933.
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| Animal Protocol |
Compound PF-06260933 (10 mg/kg, dissolved in dH2O) is orally administered to 8 to 10-week-old male Apoe-/- mice twice daily for 6 weeks. Male Ldlr-/- mice are subjected to a high-fat diet (HFD) for ten weeks prior to medication administration. Male Ldlr-/- mice aged 8 to 10 weeks receive the same dosage of compound PF-06260933 for 10 weeks. In all studies, the vehicle control is the oral administration of water. CO2 inhalation and bilateral pneumothorax are used to put mice to sleep.
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| References |
| Molecular Formula |
C16H13CLN4
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|---|---|---|
| Molecular Weight |
296.08
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| Exact Mass |
296.08
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| Elemental Analysis |
C, 64.76; H, 4.42; Cl, 11.95; N, 18.88
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| CAS # |
1811510-56-1
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| Related CAS # |
1883548-86-4 (2HCl);1811510-56-1;2118243-34-6 (HCl);
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| PubChem CID |
118701008
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| Appearance |
White to off-white solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
332
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KHPCIHZXOGHCLY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H13ClN4/c17-13-4-1-10(2-5-13)14-7-12(9-21-16(14)19)11-3-6-15(18)20-8-11/h1-9H,(H2,18,20)(H2,19,21)
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| Chemical Name |
5-(6-aminopyridin-3-yl)-3-(4-chlorophenyl)pyridin-2-amine
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.42 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 (8.42 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 | 3.3775 mL | 16.8873 mL | 33.7747 mL | |
| 5 mM | 0.6755 mL | 3.3775 mL | 6.7549 mL | |
| 10 mM | 0.3377 mL | 1.6887 mL | 3.3775 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.
Pharmacological MAP4K4 inhibition ameliorates atherosclerosis.Nat Commun.2015 Dec 21;6:8995. |
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(a) Effects of16(PF-06260933 )on LPS-induced TNFα levels in C57-BL/6J mice). (b) Effects of16on glycemic control inob/obmice.ACS Med Chem Lett.2015 Oct 6;6(11):1128-33. |
 Total and free plasma concentration of16(PF-06260933 )after PO dosing (10 mg/kg) to mice.ACS Med Chem Lett.2015 Oct 6;6(11):1128-33. |
 Heat map obtained from an Invitrogen selectivity panel (% inhibition of kinases tested @1 μM).ACS Med Chem Lett.2015 Oct 6;6(11):1128-33. |
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ACS Med Chem Lett.2015 Oct 6;6(11):1128-33. |
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