AZD7545 is a potent, competitive, selective PDHK2 (pyruvate dehydrogenase kinase 2) inhibitor with IC50s of 36.8 nM, 6.4 nM for PDHK1 and PDHK2, respectively.
体外研究
AZD7545 (10 μM; 90 hours for BRAF human melanoma cells and 120 hours for NRAS human melanoma cells) specifically suppresses growth of cells harboring BRAF and NRAS mutations as well as in inhibitor-resistant human melanoma.
Cell Proliferation Assay
Cell Line:
Human melanoma cells lines of BRAF (A375, IGR37) and NRAS (SKMel30, IPC298, MelJuso)
Concentration:
10 μM
Incubation Time:
90 hours (BRAF human melanoma cells) and 120 hours (NRAS human melanoma cells)
Result:
Mediated growth suppression of BRAF mutant and NRAS human melanoma cells.
体内研究
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.
Animal Model:
Obese male (fa/fa) Zucker rats
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.
分子式
C19H18ClF3N2O5S
分子量
478.87
CAS号
252017-04-2
运输条件
Room temperature in continental US; may vary elsewhere.