Abstract
Inhibition of ACAT, the enzyme which catalyses the intracellular formation of cholesteryl esters, is a very attractive target for the treatment of hypercholesterolaemia and atherosclerosis. However, in the past years many ACAT inhibitors gave disappointing results in clinical trials showing very low efficacy. In addition, their development was affected by the adrenotoxicity observed in many compounds. The discovery of two isoforms of the enzyme, namely ACAT1 and ACAT2, with different substrate specificity and different potential function, offers a precious information for planning selective inhibitors with reduced secondary effects. Today some potent, bioavailable and non adrenotoxic ACAT inhibitors are under clinical evaluation. Amongst others, a very promising compound is Avasimibe, presently in phase III clinical trials as anti-hyperlipidemic and anti-atherosclerotic agent. Finally, ACAT inhibitors have recently been proposed for the treatment of Alzheimers disease.
Keywords: cholesterol acyl-coa, cholesterol acyl transferase, atherosclerosis, anilide and urea derivatives, adrenotoxicity, alzheimer disease
Mini-Reviews in Medicinal Chemistry
Title: Selective ACAT Inhibitors as Promising Antihyperlipidemic, Antiatherosclerotic and Anti-Alzheimer Drugs
Volume: 3 Issue: 6
Author(s): M. P. Giovannoni, V. Dal Piaz, C. Vergelli and D. Barlocco
Affiliation:
Keywords: cholesterol acyl-coa, cholesterol acyl transferase, atherosclerosis, anilide and urea derivatives, adrenotoxicity, alzheimer disease
Abstract: Inhibition of ACAT, the enzyme which catalyses the intracellular formation of cholesteryl esters, is a very attractive target for the treatment of hypercholesterolaemia and atherosclerosis. However, in the past years many ACAT inhibitors gave disappointing results in clinical trials showing very low efficacy. In addition, their development was affected by the adrenotoxicity observed in many compounds. The discovery of two isoforms of the enzyme, namely ACAT1 and ACAT2, with different substrate specificity and different potential function, offers a precious information for planning selective inhibitors with reduced secondary effects. Today some potent, bioavailable and non adrenotoxic ACAT inhibitors are under clinical evaluation. Amongst others, a very promising compound is Avasimibe, presently in phase III clinical trials as anti-hyperlipidemic and anti-atherosclerotic agent. Finally, ACAT inhibitors have recently been proposed for the treatment of Alzheimers disease.
Export Options
About this article
Cite this article as:
Giovannoni P. M., Piaz Dal V., Vergelli C. and Barlocco D., Selective ACAT Inhibitors as Promising Antihyperlipidemic, Antiatherosclerotic and Anti-Alzheimer Drugs, Mini-Reviews in Medicinal Chemistry 2003; 3 (6) . https://dx.doi.org/10.2174/1389557033487890
DOI https://dx.doi.org/10.2174/1389557033487890 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Neurogenesis and Sensorimotor Gating: Bridging a Microphenotype and an Endophenotype
Current Molecular Medicine Supplements, Diets and Other Complementary and Alternative Interventions in Adolescent Mental Health
Adolescent Psychiatry Non-Pharmacological Approaches to the Prevention and Treatment of Alzheimer’s Disease with Respect to the Rising Treatment Costs
Current Alzheimer Research Synthesis and Antihypertensive Activity of Novel Quinazolin-4(3H)-one Derivatives
Central Nervous System Agents in Medicinal Chemistry Antioxidant Status and Energy State of Erythrocytes in Alzheimer Dementia: Probing for Markers
CNS & Neurological Disorders - Drug Targets Editorial - The As and Ms of Alzheimers Disease
Current Alzheimer Research Prediction of Drug-Drug Interactions Related to Inhibition or Induction of Drug-Metabolizing Enzymes
Current Topics in Medicinal Chemistry Syndromes Caused by the Mutations in GLI3 Gene
Current Pediatric Reviews Hair Loss Prevention by a Scalp Cooling Device in Early Breast Cancer Patients: The Poliambulanza Preliminary Experience
Reviews on Recent Clinical Trials Editorial [Hot Topic: Chemokine Inhibitors as Anti-Inflammatory Drugs (Executive Editor: David J. Grainger)]
Mini-Reviews in Medicinal Chemistry New Patents on Topical Anesthetics
Recent Patents on Inflammation & Allergy Drug Discovery Timing is Everything
Current Neurovascular Research Oxidative Stress: The Old Enemy in Alzheimers Disease Pathophysiology
Current Alzheimer Research Antenatal Depression; its Prevalence of Positive Screen and the Associating Risk Factors Including Labor and Neonatal Outcome
Current Women`s Health Reviews The Ubiquitin-Proteasome System (UPS) and the Mechanism of Action of Bortezomib
Current Pharmaceutical Design Meet Our Section Editor
Current Drug Discovery Technologies Pharmacological Perspectives of Ayurvedic Herbs <i>viz. Alstonia scholaris</i> L., <i>Picrorhiza kurroa, Swertia chirata</i> and <i>Caesalpinia crista</i> Against COVID- 19: A Mini-Review
Mini-Reviews in Organic Chemistry Can we Target the Chemokine Network for Cancer Therapeutics?
Current Cancer Drug Targets Pharmacokinetics of Darolutamide in Mouse - Assessment of the Disposition of the Diastereomers, Key Active Metabolite and Interconversion Phenomenon: Implications to Cancer Patients
Drug Metabolism Letters Metformin: A Growing Journey from Glycemic Control to the Treatment of Alzheimer’s Disease and Depression
Current Medicinal Chemistry