| Size | Price | Stock | Qty |
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| 1mg |
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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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| 250mg | |||
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| Targets |
AMPK (AMP-activated protein kinase). PF-249 is a β1-selective AMPK activator with an EC50 of 12 nM for AMPK α1β1γ1. It is a potent and orally active allosteric AMPK activator.
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| ln Vitro |
PF-249 is a potent and orally active allosteric AMPK activator with an EC50 of 12 nM for recombinant AMPK α1β1γ1. It is a β1-selective AMPK activator. PF-06685249 exhibited robust activation of AMPK in rat kidneys.
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| ln Vivo |
PF-249 (PF-06685249) is an orally active AMPK activator. It can be used in studies about diabetic nephropathy. PF-06685249 exhibited robust activation of AMPK in rat kidneys as well as desirable orally bioavailable absorption, low plasma clearance, and negligible renal clearance in preclinical species.
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| Enzyme Assay |
AMPK activation assays are performed using recombinant AMPK complexes (α1β1γ1). The enzyme is incubated with a peptide substrate (e.g., SAMS peptide) and [γ-32P]ATP or fluorescently labeled ATP in kinase buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT). The reaction is incubated at 30°C for 30 minutes. Phosphorylated substrate is quantified by scintillation counting or fluorescence polarization. PF-249 is serially diluted and added to the reaction mixture. EC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
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| Cell Assay |
Cellular AMPK activation is evaluated in cell lines (e.g., HepG2, C2C12). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with PF-249 at various concentrations for 1-24 hours. AMPK phosphorylation (Thr172) and downstream targets (ACC, mTOR) are measured by Western blotting. Cellular energy status (ATP/AMP ratio) may be assessed. Cell viability is assessed using MTT or LDH assays. Each experiment includes known AMPK activators (e.g., AICAR) as positive controls and vehicle controls.
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| Animal Protocol |
In vivo efficacy is evaluated in rodent models of diabetic nephropathy (e.g., ZSF-1 rats, db/db mice). PF-249 is administered orally at doses determined by preclinical studies. Kidney tissue is collected for AMPK activation analysis (phosphorylation and downstream targets). Renal function markers (urinary albumin, creatinine) are measured. Blood glucose and lipid parameters are assessed. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Molecular Weight: 345.78. Formula: C17H16ClN3O3. CAS No.: 1467059-70-6. Synonyms: PF-06685249. Target: AMPK. Storage: Powder -20°C 3 years; 4°C 2 years; In solvent -80°C 6 months; -20°C 1 month. For research use only.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available. As an AMPK activator, potential toxicities may include effects on metabolism and energy homeostasis. Standard toxicity studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on metabolism, the cardiovascular system, and the kidneys. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References |
Cokorinos EC, Delmore J, Reyes AR, Albuquerque B, Kjøbsted R, Jørgensen NO, Tran JL, Jatkar A, Cialdea K, Esquejo RM, Meissen J, Calabrese MF, Cordes J, Moccia R, Tess D, Salatto CT, Coskran TM, Opsahl AC, Flynn D, Blatnik M, Li W, Kindt E, Foretz M, Viollet B, Ward J, Kurumbail RG, Kalgutkar AS, Wojtaszewski JFP, Cameron KO, Miller RA. Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice. Cell Metab. 2017 May 2;25(5):1147-1159.e10. doi: 10.1016/j.cmet.2017.04.010. PubMed PMID: 28467931.
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| Additional Infomation |
PF-249 is also known as PF-06685249. It is a β1-selective AMPK activator with an EC50 of 12 nM for AMPK α1β1γ1. It is a potent and orally active allosteric AMPK activator. It can be used in studies about diabetic nephropathy. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C17H16CLN3O3
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|---|---|
| Molecular Weight |
345.780242919922
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| Exact Mass |
345.088
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| Elemental Analysis |
C, 59.05; H, 4.66; Cl, 10.25; N, 12.15; O, 13.88
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| CAS # |
1467059-70-6
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| Related CAS # |
1467059-70-6;
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| PubChem CID |
71767991
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| Appearance |
Off-white to gray solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
464
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)C1=NC(=C(C=C1)C2=C(C=C3C(=C2)C(=CN3)C(=O)O)Cl)OC
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| InChi Key |
MJHBRTGGZYSCHJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16ClN3O3/c1-21(2)15-5-4-9(16(20-15)24-3)10-6-11-12(17(22)23)8-19-14(11)7-13(10)18/h4-8,19H,1-3H3,(H,22,23)
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| Chemical Name |
6-Chloro-5-(6-(dimethylamino)-2-methoxypyridin-3-yl)-1H-indole-3-carboxylic acid
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| Synonyms |
PF-249 PF 249 PF249 PF-06685249 PF-06685249 PF-06685249 PF-6685249 PF-6685249 PF-6685249
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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 : ~100 mg/mL (~289.20 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 | 2.8920 mL | 14.4601 mL | 28.9201 mL | |
| 5 mM | 0.5784 mL | 2.8920 mL | 5.7840 mL | |
| 10 mM | 0.2892 mL | 1.4460 mL | 2.8920 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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