PF-07208254
Based on 1 Customer Validation
PF-07208254 is a selective, orally active allosteric inhibitor of branched-chain ketoacid dehydrogenase kinase (BDK) (IC50=110 nM, Ki=54 nM, KD=84 nM). PF-07208254 inhibits BDK-mediated BCKDH phosphorylation and enhances the catabolism of branched-chain amino acids (BCAAs) and branched-chain keto acids (BCKAs) by binding to the allosteric pocket of BDK, reducing BDK binding to BCKDH-E2 and promoting BDK degradation. PF-07208254 inhibits BDK activity in human skeletal muscle cells (IC50=540 nM) and has activity to improve cardiac function and metabolism. PF-07208254 can be used in the study of cardiometabolic diseases (e.g., heart failure, type 2 diabetes).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit: 98.46%
- CAS. Nr.: 2573122-40-2
- Formel: C7H2ClFO2S2
- Molecular Weight:236.67
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Speicherung:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
PF-07208254 inhibits BCKDH phosphorylation in human skeletal muscle cells with a cellular IC50 of 540 nM[1].
PF-07208254 (3-30 μM; 48 h) reduces the pBCKDH/BCKDH ratio and BDK protein levels in HEK293 cells in a dose-dependent manner[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:16-week-old male C57BL6/J mice, high-fat diet (HFD)-induced obese model[1]
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Dosage:30 mg/kg, 90 mg/kg
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Administration:Oral gavage, once daily, 8 weeks
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Result:Reduced glucose excursion in oral glucose tolerance test (oGTT) at day 2 and week 2, with significant reduction in AUC; decreased triglyceride content in liver (with a strong trend, p=0.06) and reduced steatosis score; lowered expression of inflammatory genes (Ccl2, Ccr2, Cd68) and fibrotic genes (Col1a1, Col1a2) in liver; decreased fasting insulin levels; caused significant, dose- and time-dependent reductions in BCAA and BCKA levels in plasma and muscle.
Chemical Information
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CAS. Nr. 2573122-40-2
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Appearance Solid
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Molecular Weight 236.67
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Formel C7H2ClFO2S2
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Color White to off-white
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SMILES
FC1=CC(SC(C(O)=O)=C2Cl)=C2S1
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Structure Classification
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Initial Source
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
DMSO : 100 mg/mL (422.53 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (10.56 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 2.5 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Reinheit & Dokumentation
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Data Sheet (276 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Roth Flach RJ, et al. Small molecule branched-chain ketoacid dehydrogenase kinase (BDK) inhibitors with opposing effects on BDK protein levels. Nat Commun. 2023 Aug 9;14(1):4812. [Content Brief]
[2]. Filipski KJ, et al. Discovery of First Branched-Chain Ketoacid Dehydrogenase Kinase (BDK) Inhibitor Clinical Candidate PF-07328948. J Med Chem. 2025 Feb 13;68(3):2466-2482. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 4.2253 mL | 21.1265 mL | 42.2529 mL | 105.6323 mL |
| 5 mM | 0.8451 mL | 4.2253 mL | 8.4506 mL | 21.1265 mL | |
| 10 mM | 0.4225 mL | 2.1126 mL | 4.2253 mL | 10.5632 mL | |
| 15 mM | 0.2817 mL | 1.4084 mL | 2.8169 mL | 7.0422 mL | |
| 20 mM | 0.2113 mL | 1.0563 mL | 2.1126 mL | 5.2816 mL | |
| 25 mM | 0.1690 mL | 0.8451 mL | 1.6901 mL | 4.2253 mL | |
| 30 mM | 0.1408 mL | 0.7042 mL | 1.4084 mL | 3.5211 mL | |
| 40 mM | 0.1056 mL | 0.5282 mL | 1.0563 mL | 2.6408 mL | |
| 50 mM | 0.0845 mL | 0.4225 mL | 0.8451 mL | 2.1126 mL | |
| 60 mM | 0.0704 mL | 0.3521 mL | 0.7042 mL | 1.7605 mL | |
| 80 mM | 0.0528 mL | 0.2641 mL | 0.5282 mL | 1.3204 mL | |
| 100 mM | 0.0423 mL | 0.2113 mL | 0.4225 mL | 1.0563 mL |
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