AZD7545_product_DataBase

Bioactivity

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[1].

Target

IC50: 6.4 nM (PDHK2), 36.8 nM (PDHK1)

Invitro

AZD7545 (10 μM; 90 hours for BRAFV600E 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]. Cell Proliferation Assay[2] Cell Line:

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]. Animal Model:

Name

AZD7545

CAS

252017-04-2

Formula

C19H18ClF3N2O5S

Molar Mass

478.87

Appearance

Solid

Transport

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

Reference

[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.

PeptideDB

AZD7545

CAS: 252017-04-2 F: C19H18ClF3N2O5S W: 478.87