11β-HSD1 Inhibitors for the Treatment of Type 2 Diabetes and Cardiovascular Disease

Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of type 2 diabetes mellitus. Over 170 new compounds targeting 11β-HSD1 have been developed. This article reviews the current published literature on compounds...

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Bibliographic Details
Published in:Drugs (New York, N.Y.) Vol. 73; no. 13; pp. 1385 - 1393
Main Authors: Anderson, Anna, Walker, Brian R.
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 01.09.2013
Adis International
Subjects:
11-beta-Hydroxysteroid Dehydrogenase Type 1 - antagonists & inhibitors
11-beta-Hydroxysteroid Dehydrogenase Type 1 - metabolism
Animals
Antihypertensive Agents - adverse effects
Antihypertensive Agents - pharmacology
Antihypertensive Agents - therapeutic use
Biological and medical sciences
Cardiovascular Diseases - drug therapy
Cardiovascular Diseases - enzymology
Cardiovascular Diseases - immunology
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - enzymology
Diabetes Mellitus, Type 2 - immunology
Diabetes. Impaired glucose tolerance
Drugs, Investigational - adverse effects
Drugs, Investigational - pharmacology
Drugs, Investigational - therapeutic use
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Enzyme Inhibitors - adverse effects
Enzyme Inhibitors - pharmacology
Enzyme Inhibitors - therapeutic use
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Humans
Hypoglycemic Agents - adverse effects
Hypoglycemic Agents - pharmacology
Hypoglycemic Agents - therapeutic use
Hypolipidemic Agents - adverse effects
Hypolipidemic Agents - pharmacology
Hypolipidemic Agents - therapeutic use
Immunity, Innate - drug effects
Internal Medicine
Leading Article
Medical sciences
Medicine
Medicine & Public Health
Metabolic Syndrome - drug therapy
Metabolic Syndrome - enzymology
Metabolic Syndrome - immunology
Molecular Targeted Therapy - adverse effects
Pharmacology/Toxicology
Pharmacotherapy
DHEA
Carbenoxolone
Glycyrrhetinic Acid
Glycaemic Control
Cortisol
Endocrinopathy
Type 2 diabetes
Treatment
Enzyme
11β-Hydroxysteroid dehydrogenase
Metabolic diseases
Cardiovascular disease
Inhibitor
Oxidoreductases
Review
ISSN:0012-6667, 1179-1950, 1179-1950
Online Access:Get full text
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Summary:Inhibition of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of type 2 diabetes mellitus. Over 170 new compounds targeting 11β-HSD1 have been developed. This article reviews the current published literature on compounds that have reached phase II clinical trials in patients with type 2 diabetes, and summarises the preclinical evidence that such agents may be useful for associated conditions, including peripheral vascular disease, coronary artery disease and cognitive decline. In clinical trials, 11β-HSD1 inhibitors have been well tolerated and have improved glycaemic control, lipid profile and blood pressure, and induced modest weight loss. The magnitude of the effects are small relative to other agents, so that further development of 11β-HSD1 inhibitors for the primary therapeutic indication of type 2 diabetes has stalled. Ongoing programmes are focused on additional benefits for cognitive function and other cardiovascular risk factors.
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ISSN:0012-6667
1179-1950
1179-1950
DOI:10.1007/s40265-013-0112-5