AZD 4017

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AZD4017 是一种有效、选择性、可口服生物利用的人 11β-HSD1，IC50 为 7 nM。

AZD4017 is a potent, selective, and orally bioavailable human 11β-HSD1 with IC50 of 7 nM, shows no significant activity against 11β-HSD1 and 17β-HSD1, 17β-HSD3 (IC50>30 uM); AZD4017 is inactive (<25% inhibition at 10 μM) against Cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), and lower potency against the mouse, rat and dog 11β-HSD1 (IC50=750-4000 nM); demonstrates the dose dependent inhibition of 11β-HSD1 in vivo.Cushing Disease Phase 2 Clinical.

AZD 4017 displays excellent selectivity versus the related enzymes 11-βHSD2, 17β-HSD1, 17β-HSD3 (all IC50>30 μM) and 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. 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.

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, demonstrating the dose dependent inhibition of 11β-HSD1 by AZD 4017 in this model.

AZD4017

Metabolic Enzyme/Protease

11β-HSD

11β-HSD

Endocrinology

Cushing Disease

1024033-43-9

419.58

C22H33N3O3S

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (297.92 mM)

O=C(O)C[C@H]1CN(C2=NC(SCCC)=C(C(NC3CCCCC3)=O)C=C2)CCC1

2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid

(-20℃)

With Ice Pack

≥ 2 years