Related Experiment Video
Updated: May 30, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Structure-based design and synthesis of 1,3-oxazinan-2-one inhibitors of 11β-hydroxysteroid dehydrogenase type 1
Zhenrong Xu1, Colin M Tice, Wei Zhao
1Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, Pennsylvania 19034, USA.
Abstract:
Structure based design led directly to 1,3-oxazinan-2-one 9a with an IC(50) of 42 nM against 11β-HSD1 in vitro. Optimization of 9a for improved in vitro enzymatic and cellular potency afforded 25f with IC(50) values of 0.8 nM for the enzyme and 2.5 nM in adipocytes. In addition, 25f has 94% oral bioavailability in rat and >1000× selectivity over 11β-HSD2. In mice, 25f was distributed to the target tissues, liver, and adipose, and in cynomolgus monkeys a 10 mg/kg oral dose reduced cortisol production by 85% following a cortisone challenge.
Related Concept Videos
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
Drug Metabolism: Phase I Reactions
Antihypertensive Drugs: Thiazide-Class Diuretics
Enzyme Inhibition
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes: