[CAS NO. 1024033-43-9] AZD4017
PRODUCTS SPECIFICATIONS [1024033-43-9]
DESCRIPTION [1024033-43-9]
Overview
| MDL | MFCD25976912 |
|---|---|
| Molecular Weight | 419.58 |
| Molecular Formula | C22H33N3O3S |
| SMILES | O=C(O)C[C@H]1CN(C2=NC(SCCC)=C(C(NC3CCCCC3)=O)C=C2)CCC1 |
Summary
AZD 4017 is a potent, selective 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) inhibitor, with an IC 50 of 7 nM.
IC50 & Target
IC50: 7 nM (11β-HSD1) [1] .
In Vitro
AZD 4017 displays excellent selectivity versus the related enzymes 11-βHSD2, 17β-HSD1, 17β-HSD3 (all IC 50 >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 (IC 50 =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 (IC 50 =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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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×IC 50 in the mouse, demonstrating the dose dependent inhibition of 11β-HSD1 by AZD 4017 in this model [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00791752 | AstraZeneca |
Healthy
|
November 2008 | Phase 1 |
| NCT03313297 | University of Leeds |
Diabetes Mellitus, Type 2
|
April 10, 2018 | Phase 2 |
| NCT03111810 | University of Oxford|AstraZeneca |
Iatrogenic Cushing´s Disease
|
May 25, 2017 | Phase 2 |
| NCT00841048 | AstraZeneca |
Diabetes Mellitus Type 2
|
February 2009 | Phase 1 |
| NCT00799747 | AstraZeneca |
Healthy
|
December 2008 | Phase 1 |
| NCT02017444 | University of Birmingham |
Idiopathic Intracranial Hypertension
|
April 25, 2014 | Phase 2 |
| NCT01096004 | AstraZeneca |
Obesity
|
March 2010 | Phase 1 |
| NCT01173471 | AstraZeneca |
Raised Intraocular Pressure
|
December 2010 | Phase 2 |
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 : 125 mg/mL ( 297.92 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.3833 mL | 11.9167 mL | 23.8334 mL |
| 5 mM | 0.4767 mL | 2.3833 mL | 4.7667 mL |
| 10 mM | 0.2383 mL | 1.1917 mL | 2.3833 mL |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.96 mM); Clear solution