PF-06260933 2HCl

Alias: PF-06260933 2HCl; PF 06260933 2HCl; PF06260933 2HCl;PF-06260933 dihydrochloride; PF 06260933 dihydrochloride; PF06260933dihydrochloride

Cat No.:V3216 Purity: ≥98%

COA Product Data Instructions for use SDS

PF-06260933 2HCl Chemical Structure CAS No.: 1883548-86-4
Product category: Others 2

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of PF-06260933 2HCl:

PF-06260933

Official Supplier of:

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

PF-06260933 is a highly selective small-molecule inhibitor of MAP4K4 (Mitogen-activated protein kinase kinase kinase kinase 4) with IC50 values of 3.7 and 160 nM for cell-freel assay (kinase) and cell assay, respectively. It also inhibits MINK and TNIK with IC50 values of 8 and 13 nM, respectively. PF-06260933 has been reported to improve fasting hyperglycemia in mice. Recent studies in adipose tissue, pancreas, muscle, and macrophages suggest that MAP4K4, a serine/threonine protein kinase may be a viable target for antidiabetic drugs. As part of the evaluation of MAP4K4 as a novel antidiabetic target, PF-6260933.

Biological Activity I Assay Protocols (From Reference)

ln Vitro

In vitro activity: PF-06260933 is a highly selective small-molecule inhibitor of MAP4K4 with IC50 values of 3.7 and 160 nM for cell-freel assay (kinase) and cell assay, respectively. It also inhibits MINK and TNIK with IC50 values of 8 and 13 nM, respectively. PF-06260933 has been reported to improve fasting hyperglycemia in mice. Recent studies in adipose tissue, pancreas, muscle, and macrophages suggest that MAP4K4, a serine/threonine protein kinase may be a viable target for antidiabetic drugs. As part of the evaluation of MAP4K4 as a novel antidiabetic target, PF-6260933.

Kinase Assay: Aortas were lysed in 1% NP-40, 50 mM Tris pH 7.4, 150 mM NaCl, 50 mM EDTA with 1 × HALT protease and phosphatase inhibitors (Thermo Scientific) and immunoprecipitated with Bethyl MAP4K4 antibodies (503 A; 1 μg) or normal rabbit IgG (Cell Signaling 2729; 1 μg). Myelin basic protein (MBP) (1 μg) and 10 μCi of [γ-32P]ATP were added to the immunoprecipitates and 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 separated by 12% SDS–polyacrylamide gel electrophoresis and visualized by autoradiography.

Cell Assay: HUVECs are maintained in EGM2 media at 37°C and 5% CO2. HUVECs or peritoneal macrophages are treated with vehicle or PF-06260933 in vitroto determine whether pharmacological inhibition of MAP4K4 alteres MAPK signalling in response to TNF-α

ln Vivo

At 6–8 weeks of age, male flox/flox and flox/flox/cre+ littermates were injected with 1 mg tamoxifen per day in corn oil for 5 days. At 5–6 weeks of age (KD mice) or 2 weeks after tamoxifen injection (flox mice), the mice were fed chow or WD (0.2% cholesterol, TD 88137, Harlan Laboratories) for 16 weeks. Compound PF-06260933 (10 mg kg−1, dissolved in dH2O) was orally administered to 8–10-week-old male ApoE−/− mice twice daily for 6 weeks. Ldlr−/− male mice (B6.129S7-Ldlrtm1Her/J, Jackson Laboratories, 8–10 weeks old) were placed on HFD (1.25% cholesterol, TD96121, Harlan Laboratories) for 10 weeks before drug administration. Compound PF-06260933 was administered to male 8–10-week-old Ldlr−/− mice as above for 10 weeks. Oral administration of water was used as vehicle control in all studies. Mice were euthanized by CO2 inhalation followed by bilateral pneumothorax. No statistical methods were used to predict sample size, no randomization was performed and the investigations were not blinded during the knockout animal analyses, but were blinded during the drug treatment analyses.

Animal Protocol

Dissolved in dH2O; 10 mg/kg; orally administered

6–8 weeks of age, male flox/flox and flox/flox/cre+ littermates

References

ACS Med Chem Lett.2015 Oct 6;6(11):1128-33;Nat Commun.2015 Dec 21;6:8995.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C16H15CL3N4
Molecular Weight	369.67610001564
CAS #	1883548-86-4
Related CAS #	1883548-86-4 (2HCl);1811510-56-1;2118243-34-6 (HCl);
SMILES	ClC1C=CC(=CC=1)C1C(N)=NC=C(C2C=NC(=CC=2)N)C=1.Cl.Cl
Synonyms	PF-06260933 2HCl; PF 06260933 2HCl; PF06260933 2HCl;PF-06260933 dihydrochloride; PF 06260933 dihydrochloride; PF06260933dihydrochloride
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)

Solubility Data

Solubility (In Vitro)

DMSO: >50 mg/mL

Water:

Ethanol:

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7050 mL	13.5252 mL	27.0504 mL
	5 mM	0.5410 mL	2.7050 mL	5.4101 mL
	10 mM	0.2705 mL	1.3525 mL	2.7050 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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

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Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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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.

Note： (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.

Biological Data

Pharmacological MAP4K4 inhibition ameliorates atherosclerosis.Nat Commun.2015 Dec 21;6:8995.
(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.
ACS Med Chem Lett.2015 Oct 6;6(11):1128-33.