[CAS NO. 252017-04-2] AZD7545
PRODUCTS SPECIFICATIONS [252017-04-2]
DESCRIPTION [252017-04-2]
Overview
| MDL | MFCD25976792 |
|---|---|
| Molecular Weight | 478.87 |
| Molecular Formula | C19H18ClF3N2O5S |
| SMILES | O=C(N(C)C)C1=CC=C(S(=O)(C2=CC=C(NC([C@@](C)(O)C(F)(F)F)=O)C(Cl)=C2)=O)C=C1 |
Summary
AZD7545 is a potent, competitive, selective PDHK2 (pyruvate dehydrogenase kinase 2) inhibitor with IC 50 s of 36.8 nM, 6.4 nM for PDHK1 and PDHK2 , respectively [1] .
IC50 & Target
IC50: 6.4 nM (PDHK2), 36.8 nM (PDHK1) [1]
In Vitro
AZD7545 (10 μM; 90 hours for BRAF
V600E
human melanoma cells and 120 hours for NRAS
mut
human melanoma cells) specifically suppresses growth of cells harboring BRAF and NRAS mutations as well as in inhibitor-resistant human melanoma
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay [2]
| Cell Line: | Human melanoma cells lines of BRAF V600E (A375, IGR37) and NRAS mut (SKMel30, IPC298, MelJuso) |
| Concentration: | 10 μM |
| Incubation Time: | 90 hours (BRAF V600E human melanoma cells) and 120 hours (NRAS mut human melanoma cells) |
| Result: | Mediated growth suppression of BRAF V600E mutant and NRAS mut human melanoma cells. |
In Vivo
A single dose of AZD7545 (Oral administration; 10 mg/kg once a day (08:00 h) or Twice a day (08:00 and 18:00 h); for 7 days) to Wistar rats increases the proportion of liver PDH in its active, dephosphorylated form in a dose-related manner. A single dose of 10 mg/kg also significantly elevates muscle PDH activity in obese Zucker (fa/fa) rats [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Obese male (fa/fa) Zucker rats [3] |
| Dosage: | 10 mg/kg |
| Administration: | Oral administration; once a day (08:00 h) or Twice a day ( 08:00 and 18:00 h); for 7 days |
| Result: | Improved the control of blood glucose levels. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 46 mg/mL ( 96.06 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.0882 mL | 10.4412 mL | 20.8825 mL |
| 5 mM | 0.4176 mL | 2.0882 mL | 4.1765 mL |
| 10 mM | 0.2088 mL | 1.0441 mL | 2.0882 mL |
References
- [1] Morrell JA, et al. AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2. Biochem Soc Trans. 2003 Dec;31(Pt 6):1168-70.
- [2] Mayers RM, et al. AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats. Biochem Soc Trans. 2003 Dec;31(Pt 6):1165-7.
- [3] Cesi G et al. ROS production induced by BRAF inhibitor treatment rewires metabolic processes affecting cell growth of melanoma cells. Mol Cancer. 2017 Jun 8;16(1):102.