AZD 4017 是高效的、选择性的11β-HSD1抑制剂，IC50为 7 nM。

AZD 4017 is an inhibitor of 11β-Hydroxysteroid Dehydrogenase Type 1(11β-HSD1) (IC50: 7 nM).

AZD 4017 is shown to be a potent inhibitor in this key target tissue (IC50=0.002 μM) in good agreement with the enzyme potency, thus providing some confidence that AZD 4017 is not restricted from adipose tissue by the fact that it was acidic[1]. AZD 4017 displays excellent selectivity versus the related enzymes 11-βHSD2, 17β-HSD1, 17β-HSD3 (all IC50>30 μM). It shows no measurable activity against the glucocorticoid and mineralocorticoid receptors. Despite having high potency for the human form of 11β-HSD1, AZD 4017 shows much reduced activity across species with the exception of cynomolgous monkey (IC50=0.029 μM). Additionally, as it is believed that adipose is a key target organ, inhibition of 11β-HSD1 activity is measured in isolated human adipocytes from nondiabetic volunteers.

Since AZD 4017 has lower potency against the mouse enzyme, only a limited number of preclinical pharmacodynamic measurements are performed. Increasing the dose further led to a maximal effect of approximately 70% inhibition at 1500 mg/kg, equivalent to 10×IC50 in the mouse. Which demonstrating the dose dependent inhibition of 11β-HSD1 by AZD 4017 in this model[1].

1024033-43-9

C22H33N3O3S

419.58

DMSO:125 mg/mL (297.92 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years