Bempedoic Acid and the Fraudulent Fatty Acid Family: The Gold Rush to Cardiovascular Therapies in the New Millennium

Oniciu, Daniela C.; Myers, Jennifer L.

doi:10.1021/acs.oprd.0c00501

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…gemcabene [ 16 ], characterized by long-chain hydrocarbons with terminal hydroxymethylene and carboxylic acid groups. Among these, bempedoic acid proved to have an optimal pharmacokinetic and pharmacodynamic profile [ 17 ].…”

Section: Why a New Oral Non-statin Cholesterol-lowering Drug?mentioning

confidence: 99%

Bempedoic Acid: for Whom and When

Ruscica

Sirtori

Carugo

et al. 2022

Curr Atheroscler Rep

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Purpose of Review The aim of creating an orally active non-statin cholesterol-lowering drug was achieved with bempedoic acid, a small linear molecule providing both a significant low-density lipoprotein cholesterol (LDL-C) reduction and an anti-inflammatory effect by decreasing high-sensitivity C-reactive protein. Bempedoic acid antagonizes ATP citrate-lyase, a cytosolic enzyme upstream of HMGCoA reductase which is the rate-limiting step of cholesterol biosynthesis. Bempedoic acid is a pro-drug converted to its active metabolite by very-long-chain acyl-CoA synthetase 1 which is present mostly in the liver and absent in skeletal muscles. This limits the risk of myalgia and myopathy. The remit of this review is to give clinical insights on the safety and efficacy of bempedoic acid and to understand for whom it should be prescribed. Recent Findings Bempedoic acid with a single daily dose (180 mg) reduces LDL-C by a mean 24.5% when given alone, by 18% when given on top of a major statin and by 38–40% when given in a fixed-dose combination with ezetimibe. Bempedoic acid does not lead to the risk of new-onset diabetes, and moderately improves the glycaemic profile. Summary The extensive knowledge on bempedoic acid mechanism, metabolism and side effects has led to an improved understanding of the potential benefits of this agent and offers a possible alternative to cardiologists and clinical practitioners somewhat worn out today by the occurrence of the muscular side effects of statins.

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Section: Why a New Oral Non-statin Cholesterol-lowering Drug?mentioning

confidence: 99%

Bempedoic Acid: for Whom and When

Ruscica

Sirtori

Carugo

et al. 2022

Curr Atheroscler Rep

View full text Add to dashboard Cite

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“…The chemical structure of bempedoic acid resembles an α,ω-dicarboxylic acid (14). In a recent study, the authors identified a series of odd-chain fatty acids as HDAC6 inhibitors, which motivated the exploration of the HDAC6 inhibitory effects of new fatty acid candidates (15).…”

Section: Introductionmentioning

confidence: 99%

Repurposing bempedoic acid as a histone deacetylase 6 inhibitor

2023

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The dysregulation of the activity of histone deacetylase 6 (HDAC6) is observed in a number of human diseases. Targeting HDAC6 has been identified as an ideal treatment strategy in epigenetic-based therapies. Bempedoic acid is an FDA-approved cholesterol-lowering medication. In the present study, bempedoic acid was repurposed as an HDAC6 inhibitor for the first time, at least to the best of our knowledge. Bempedoic acid inhibited the activity of HDAC6 in vitro with an IC 50 value of ~0.8 mM. In silico analysis predicted the formation of hydrogen bonds and hydrophobic interactions between HDAC6 residues and bempedoic acid, which may be attributed to its HDAC6 inhibitory potential. The results of the present study provide new opportunities to bring bempedoic acid into epigenetic-based drug discovery platforms.

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Bempedoic Acid and Statins in Lipid-Lowering Strategy: Which Came First, the Egg or the Chicken?

Natale

Molinari

Franzese

et al. 2023

Future Pharmacology

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The goal in cardiovascular prevention is the reduction of morbidity and mortality through the promotion of healthy lifestyles in the general population. The management of modifiable risk factors with pharmacological and non-pharmacological interventions, based on the individual risk is the first strategy suggested by the current guidelines. Several epidemiological studies have clearly shown the direct correlation between high levels of low-density lipoprotein cholesterol (LDL-C) and incidence of cardiovascular diseases. On the other hand, numerous randomized clinical studies have reported a huge benefit in terms of major cardiovascular events achievable by the reduction of LDL-C, thus supporting the notion that “the lower is better”. Among the lipid-lowering strategies, statins are the drugs of choice in cardiovascular prevention, at both primary and secondary level. To achieve the ambitious targets suggested by the current guidelines, other lipid-lowering therapies are currently available in addition to statins, such as ezetimibe the inhibitors of the PCSK9. Pharmacological research has recently led to the development of a new drug, the bempedoic acid, which further enrich the available therapies. This drug also acts on the biosynthesis of cholesterol but at upstream level than statins. From the biochemical point of view, it has the potential to be considered before the statin with consequent titration of statins to achieve the desirable LDL-C target. In the present review, the biochemical and pharmacological characteristics of bempedoic acid are discussed. An overview of the clinical data that support its use in the management of the cardiovascular patient and its allocation in the lipid-lowering scenario will be also provided.

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Bempedoic Acid and the Fraudulent Fatty Acid Family: The Gold Rush to Cardiovascular Therapies in the New Millennium

Cited by 3 publications

References 21 publications

Bempedoic Acid: for Whom and When

Bempedoic Acid: for Whom and When

Repurposing bempedoic acid as a histone deacetylase 6 inhibitor

Bempedoic Acid and Statins in Lipid-Lowering Strategy: Which Came First, the Egg or the Chicken?

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