Lovastatin

Identification

Summary

Lovastatin is an HMG-CoA reductase inhibitor used to lower LDL cholesterol and reduce the risk of cardiovascular disease and associated conditions, including myocardial infarction and stroke.

Brand Names

Advicor, Altoprev

Generic Name

Lovastatin

DrugBank Accession Number

DB00227

Background

Lovastatin, also known as the brand name product Mevacor, is a lipid-lowering drug and fungal metabolite derived synthetically from a fermentation product of Aspergillus terreus.¹ Originally named Mevinolin, lovastatin belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage abnormal lipid levels by inhibiting the endogenous production of cholesterol in the liver.² More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase,¹² which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions involved in the production of several compounds involved in lipid metabolism and transport including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as "bad cholesterol"), and very low-density lipoprotein (VLDL). Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.^13,14

Lovastatin and other drugs from the statin class of medications including atorvastatin, pravastatin, rosuvastatin, fluvastatin, and simvastatin are considered first-line options for the treatment of dyslipidemia.^13,14 Increasing use of the statin class of drugs is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world.¹⁵ Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.^13,16 Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.^{17,18,19,20,21,22} Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.^13,14 Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.^24,23

While all statin medications are considered equally effective from a clinical standpoint, rosuvastatin is considered the most potent; doses of 10 to 40mg rosuvastatin per day were found in clinical studies to result in a 45.8% to 54.6% decrease in LDL cholesterol levels, while lovastatin has been found to have an average decrease in LDL-C of 25-40%.^{5,25,26,22,27} Potency is thought to correlate to tissue permeability as the more lipophilic statins such as lovastatin are thought to enter endothelial cells by passive diffusion, as opposed to hydrophilic statins such as pravastatin and rosuvastatin which are taken up into hepatocytes through OATP1B1 (organic anion transporter protein 1B1)-mediated transport.^31,28 Despite these differences in potency, several trials have demonstrated only minimal differences in terms of clinical outcomes between statins.^22,20

Type

Small Molecule

Groups

Approved, Investigational

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Lovastatin (DB00227)

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Weight

Average: 404.5396
Monoisotopic: 404.256274262

Chemical Formula

C₂₄H₃₆O₅

Synonyms

• (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(2R,4R)-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl (S)-2-methyl-butyrate
• 2β,6α-dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinic acid lactone
• 6-alpha-methylcompactin
• 6alpha-methylcompactin
• 6α-methylcompactin
• Lovastatin
• Lovastatina
• Lovastatine
• Lovastatinum
• Mevinolin

External IDs

• L-154803
• MK-803
• ML-530B

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Pharmacology

Indication

Lovastatin is indicated to reduce the risk of myocardial infarction, unstable angina, and the need for coronary revascularization procedures in individuals without symptomatic cardiovascular disease, average to moderately elevated total-C and LDL-C, and below average HDL-C. It is indicated as an intervention alternative in individuals presenting dyslipidemia at risk of developing atherosclerotic vascular disease. The administration of this agent should be accompanied by the implementation of a fat and cholesterol-restricted diet.⁴³

Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Lovastatin is indicated as an adjunct to diet for the reduction of elevated total-C and LDL-C levels in patients with primary hypercholesterolemia (Types IIa and IIb2), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate.^43,44

Lovastatin is also indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower total-C and LDL-C to target levels.⁴³

Lovastatin is indicated as an adjunct to diet to reduce total-C, LDL-C and apolipoprotein B levels in adolescent boys and girls with Heterozygous Familial Hypercholesterolemia (HeFH) who are at least one year post-menarche, 10 to 17 years of age, with HeFH if after an adequate trial of diet therapy the following findings are present: LDL-C remains greater than 189 mg/dL or LDL-C remains greater than 160 mg/dL and there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the adolescent patient.

Before administering lovastatin, it is important to rule out the presence of secondary causes of hypercholesterolemia and a lipid profile should be performed.

Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD. Statin-indicated conditions include diabetes mellitus, clinical atherosclerosis (including myocardial infarction, acute coronary syndromes, stable angina, documented coronary artery disease, stroke, trans ischemic attack (TIA), documented carotid disease, peripheral artery disease, and claudication), abdominal aortic aneurysm, chronic kidney disease, and severely elevated LDL-C levels.^13,14

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Adjunct therapy in management of	Apolipoprotein		••••••••••••		••• • ••• ••••• ••••• •••• ••••••••••••• •••••••••••• •••••••• •••••••••••••••••••• ••••••• ••• • ••• ••••• ••• •••••••• ••••••• •• •••••••••••••• •••••••• • •••• •••••••••••••• ••• • ••• ••••• ••• ••• •••••••••••••• •••• •••••••	••••••
Adjunct therapy in management of	Apolipoprotein		••••••••••••		••••• •••••••••••••• ••••••• ••••••••••••••••••••	••••••• ••••••• •••••••• •••••••
Adjunct therapy in management of	Cholesterol, ldl		••••••••••••		••• • ••• ••••• ••••• •••• ••••••••••••• ••• • ••• ••••• ••• •••••••• ••••••• •• •••••••••••••• •••••••• •••••••••••• •••••••• •••••••••••••••••••• ••••••• ••• • ••• ••••• ••• ••• •••••••••••••• •••• •••••••• • •••• •••••••••••••	••••••
Adjunct therapy in management of	Cholesterol, ldl		••••••••••••		••••••• ••••••••••••••••••••• ••••• •••••••••••••	••••••• ••••••• •••••••• •••••••
Adjunct therapy in management of	Coronary artery atherosclerosis		••••••••••••		•••••••• ••••• ••••••• •••••	••••••• ••••••• •••••••• •••••••

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Pharmacodynamics

Lovastatin is an oral antilipemic agent which reversibly inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, lovastatin reduces the risk of cardiovascular morbidity and mortality.^5,13,14,30

Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.¹³ Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.^{17,18,19,20,21} Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.^13,14 Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.^5,24,23 Clinical studies have shown that lovastatin reduces LDL-C and total cholesterol by 25-40%.⁵ The 50% inhibitory dose is known to be of 46 mcg/kg which is translated into a reduction of approximately 30% of plasma cholesterol.²

Myopathy/Rhabdomyolysis

Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is dose-related and is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. In a clinical study (EXCEL)³⁰ in which patients were carefully monitored and some interacting drugs were excluded, there was one case of myopathy among 4933 patients randomized to lovastatin 20 to 40 mg daily for 48 weeks, and 4 among 1649 patients randomized to 80 mg daily.

Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. Chinese patients may also be at increased risk for myopathy. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued.

The risk of myopathy during treatment with lovastatin may be increased with concurrent administration of interacting drugs such as fenofibrate, niacin, gemfibrozil, cyclosporine, and strong inhibitors of the CYP3A4 enzyme. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with colchicine, and caution should therefore be exercised when prescribing these two medications together.^43,44

Real-world data from observational studies has suggested that 10-15% of people taking statins may experience muscle aches at some point during treatment.³⁸

Liver Dysfunction

Persistent increases (to more than 3 times the upper limit of normal) in serum transaminases occurred in 1.9% of adult patients who received lovastatin for at least one year in early clinical trials. When the drug was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases usually appeared 3 to 12 months after the start of therapy with lovastatin, and were not associated with jaundice or other clinical signs or symptoms.⁴³ In the EXCEL study,³⁰ the incidence of persistent increases in serum transaminases over 48 weeks was 0.1% for placebo, 0.1% at 20 mg/day, 0.9% at 40 mg/day, and 1.5% at 80 mg/day in patients on lovastatin. However, in post-marketing experience with lovastatin, symptomatic liver disease has been reported rarely at all dosages.⁴³

Mechanism of action

Lovastatin is a lactone which is readily hydrolyzed in vivo to the corresponding β-hydroxyacid and strong inhibitor of HMG-CoA reductase, a hepatic microsomal enzyme which catalyzes the conversion of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A ) to mevalonate, an early rate-limiting step in cholesterol biosynthesis.^12,2 At therapeutic lovastatin doses, HMG-CoA reductase is not completely blocked, thereby allowing biologically necessary amounts of mevalonate to be available. Because the conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol, therapy with lovastatin would not be expected to cause an accumulation of potentially toxic sterols.⁴⁴

Lovastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increase hepatic uptake of LDL. Lovastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL and a significant reduction in the risk of development of CVD and all-cause mortality.^{17,18,19,20,21}

A significant effect on LDL-C reduction was seen within 2 weeks of initiation of lovastatin, and the maximum therapeutic response occurred within 4-6 weeks. The response was maintained during continuation of therapy. Single daily doses given in the evening were more effective than the same dose given in the morning, perhaps because cholesterol is synthesized mainly at night. When therapy with lovastatin is stopped, total cholesterol has been shown to return to pre-treatment levels.⁴⁴

In vitro and in vivo animal studies also demonstrate that lovastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins.³¹ This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.

Statins have also been found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an important role in leukocyte trafficking and in T cell activation.³²

Lovastatin has been reported to have beneficial effects on certain cancers. This includes a multi-factorial stress-triggered cell death (apoptosis) and DNA degradation response in breast cancer cells.³³ It has also been shown to inhibit histone deacetylase 2 (HDAC2) activity and increase the accumulation of acetylated histone-H3 and the expression of p21(WAF/CIP) in human cancer cells, suggesting that statins might serve as novel HDAC inhibitors for cancer therapy and chemoprevention.³⁷

Target	Actions	Organism
A3-hydroxy-3-methylglutaryl-coenzyme A reductase	inhibitor	Humans
UIntegrin alpha-L	inhibitor	Humans
NHistone deacetylase 2	inhibitor	Humans

Absorption

Lovastatin Cmax was found to be 3.013ng/mL with a Tmax of 3.36 hours.⁴⁴

Plasma concentrations of total radioactivity (lovastatin plus 14C-metabolites) peaked at 2 hours and declined rapidly to about 10% of peak by 24 hours postdose. Absorption of lovastatin, estimated relative to an intravenous reference dose, in each of four animal species tested, averaged about 30% of an oral dose. In animal studies, after oral dosing, lovastatin had high selectivity for the liver, where it achieved substantially higher concentrations than in non-target tissues. Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. As a consequence of extensive hepatic extraction of lovastatin, the availability of drug to the general circulation is low and variable. In a single dose study in four hypercholesterolemic patients, it was estimated that less than 5% of an oral dose of lovastatin reaches the general circulation as active inhibitors. Following administration of lovastatin tablets the coefficient of variation, based on between-subject variability, was approximately 40% for the area under the curve (AUC) of total inhibitory activity in the general circulation.^43,44

The peak concentrations of lovastatin when a dose of 10-40 mg is administered are reported to range from 1.04-4.03 ng/ml and an AUC of 14-53 ng.h/ml. This indicates that lovastatin presents a dose-dependent pharmacokinetic profile.⁸ When lovastatin was given under fasting conditions, plasma concentrations of both active and total inhibitors were on average about two-thirds those found when lovastatin was administered immediately after a standard test meal.⁴⁴

Genetic differences in the OATP1B1 (Organic-Anion-Transporting Polypeptide 1B1) hepatic transporter encoded by the SCLCO1B1 gene (Solute Carrier Organic Anion Transporter family member 1B1) have been shown to impact lovastatin pharmacokinetics.³⁴ Evidence from pharmacogenetic studies of the c.521T>C single nucleotide polymorphism (SNP) showed that lovastatin Cmax and AUC were 340 and 286% higher, respectively, for individuals homozygous for 521CC compared to homozygous 521TT individuals.³⁵ The 521CC genotype is also associated with a marked increase in the risk of developing myopathy, likely secondary to increased systemic exposure.³⁶ Other statin drugs impacted by this polymorphism include rosuvastatin, pitavastatin, atorvastatin, simvastatin, and pravastatin.²⁸

While specific dosage instructions are not included in the available product monographs for lovastatin, individuals with the above-mentioned c.521CC OATP1B1 genotype should be monitored for development of adverse effects from increased exposure to the drug, such as muscle pain and risk of rhabdomyolysis, particularly at higher doses.

Volume of distribution

Lovastatin is able to cross the blood-brain barrier and placenta.⁴⁴

Protein binding

Both lovastatin and its β-hydroxy acid metabolite are highly bound (>95%) to human plasma proteins, largely due to its lipophilicity. Animal studies demonstrated that lovastatin crosses the blood-brain and placental barriers.^43,44

Metabolism

Lovastatin is given as a lactone prodrug and thus, in order to produce its mechanism of action, it is required to be converted to the active beta-hydroxy form. This drug activation process does not seem to be related to CYP isoenzyme activity⁷ but rather to be controlled by the activity of serum paraoxonase.¹¹

Lovastatin is metabolized by the microsomal hepatic enzyme system (Cytochrome P-450 isoform 3A4). The major active metabolites present in human plasma are the β-hydroxy acid of lovastatin, its 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives.⁴⁴ The uptake of lovastatin by the liver is enhanced by the activity of OATP1B1.⁹

Hover over products below to view reaction partners

• Lovastatin
  • 6'beta-Hydroxylovastatin
  • 3''-Hydroxylovastatin
  • 6'-exomethylene lovastatin

Route of elimination

Following an oral dose of 14C-labeled lovastatin to man, 10% of the dose was excreted in urine and 83% in feces. The latter represents absorbed drug excreted in bile, together with unabsorbed drug.⁴⁴

Half-life

Lovastatin half-life is reported to be of 13.37 hours.⁴⁴ The elimination half-life of the hydroxy acid form of lovastatin is reported to be of 0.7-3 hours.⁶

Clearance

Not Available

Adverse Effects

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Toxicity

The median lethal dose of lovastatin is higher than 15 g/m2. Five healthy human volunteers have received up to 200 mg of lovastatin as a single dose without clinically significant adverse experiences. A few cases of accidental overdosage have been reported; no patients had any specific symptoms, and all patients recovered without sequelae. The maximum dose taken was 5 to 6 g.⁴³

In carcinogenic studies, there is an increase in the incidence of hepatocellular carcinomas and adenomas, pulmonary adenomas, papilloma in non-glandular mucose in stomach and thyroid neoplasms. However, with respect to effects on fertility, lovastatin has been reported to present testicular atrophy, decreased spermatogenesis, spermatocytic degeneration and giant cell formation which derived into decreased fertility in males. Lastly, there is no evidence of mutagenicity induced by lovastatin.⁴³

Pathways

Pathway	Category
Lovastatin Action Pathway	Drug action

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Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-Benzodiazepine	The metabolism of 1,2-Benzodiazepine can be decreased when combined with Lovastatin.
Abametapir	The serum concentration of Lovastatin can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Lovastatin can be increased when combined with Abatacept.
Abemaciclib	The metabolism of Abemaciclib can be decreased when combined with Lovastatin.
Abiraterone	The metabolism of Abiraterone can be decreased when combined with Lovastatin.

Food Interactions

• Avoid grapefruit products. Grapefruit products may increase the risk for lovastatin related adverse effects such as myopathy and rhabdomyolysis.
• Take with food. Food increases bioavailability.

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Product Images

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International/Other Brands

Altocor (Andrx)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Act Lovastatin	Tablet	40 mg	Oral	TEVA Canada Limited	2004-07-28	Not applicable
Act Lovastatin	Tablet	20 mg	Oral	TEVA Canada Limited	2004-07-28	Not applicable
Altoprev	Tablet, extended release	40 mg/1	Oral	Covis Pharma US, Inc	2016-05-01	Not applicable
Altoprev	Tablet, extended release	40 mg/1	Oral	Shionogi	2002-06-26	2018-02-28
Altoprev	Tablet, extended release	60 mg/1	Oral	Physicians Total Care, Inc.	2005-07-11	2012-06-30

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Ava-lovastatin	Tablet	20 mg	Oral	Avanstra Inc	2011-08-18	2014-08-21
Ava-lovastatin	Tablet	40 mg	Oral	Avanstra Inc	2011-08-18	2014-08-21
Dom-lovastatin	Tablet	40 mg	Oral	Dominion Pharmacal	2003-02-25	Not applicable
Dom-lovastatin	Tablet	20 mg	Oral	Dominion Pharmacal	2003-02-25	Not applicable
Lovastatin	Tablet	40 mg/1	Oral	BluePoint Laboratories	2007-11-01	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Advicor	Lovastatin (20 mg/1) + Niacin (1000 mg/1)	Tablet, extended release	Oral	Kos Pharmaceuticals, Inc.	2007-02-20	2007-02-20
Advicor	Lovastatin (40 mg/1) + Niacin (1000 mg/1)	Tablet, extended release	Oral	Abbvie	2001-12-17	2018-01-31
Advicor	Lovastatin (20 mg/1) + Niacin (500 mg/1)	Tablet, extended release	Oral	Abbvie	2001-12-17	2018-03-31
Advicor	Lovastatin (20 mg/1) + Niacin (750 mg/1)	Tablet, extended release	Oral	Physicians Total Care, Inc.	2004-02-18	2011-06-30
Advicor	Lovastatin (20 mg) + Niacin (500 mg)	Tablet, extended release; Tablet, multilayer, extended release	Oral	Sepracor Pharmaceuticals Inc	2005-11-09	2012-08-02

Categories

ATC Codes

C10AA02 — Lovastatin

• C10AA — HMG CoA reductase inhibitors
• C10A — LIPID MODIFYING AGENTS, PLAIN
• C10 — LIPID MODIFYING AGENTS
• C — CARDIOVASCULAR SYSTEM

C10BA01 — Lovastatin and nicotinic acid

• C10BA — Combinations of various lipid modifying agents
• C10B — LIPID MODIFYING AGENTS, COMBINATIONS
• C10 — LIPID MODIFYING AGENTS
• C — CARDIOVASCULAR SYSTEM

Drug Categories

• Agents Causing Muscle Toxicity
• Anticholesteremic Agents
• BSEP/ABCB11 Substrates
• Cytochrome P-450 CYP2C19 Substrates
• Cytochrome P-450 CYP2C8 Inhibitors
• Cytochrome P-450 CYP2C8 Inhibitors (moderate)
• Cytochrome P-450 CYP2C8 Substrates
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
• Cytochrome P-450 CYP2D6 Inhibitors
• Cytochrome P-450 CYP2D6 Inhibitors (weak)
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (moderate)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A5 Substrates
• Cytochrome P-450 CYP3A7 Substrates
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Drugs causing inadvertant photosensitivity
• Enzyme Inhibitors
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypolipidemic Agents
• Hypolipidemic Agents Indicated for Hyperlipidemia
• Lipid Modifying Agents
• Lipid Regulating Agents
• OATP1B1/SLCO1B1 Inhibitors
• OATP1B1/SLCO1B1 Substrates
• P-glycoprotein inhibitors
• Photosensitizing Agents
• UGT1A1 Substrates
• UGT1A3 substrates
• UGT2B7 substrates

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as delta valerolactones. These are cyclic organic compounds containing an oxan-2- one moiety.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Lactones

Sub Class

Delta valerolactones

Direct Parent

Delta valerolactones

Alternative Parents

Fatty acid esters / Oxanes / Dicarboxylic acids and derivatives / Secondary alcohols / Carboxylic acid esters / Oxacyclic compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds

Substituents

Alcohol / Aliphatic heteropolycyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Delta valerolactone / Delta_valerolactone / Dicarboxylic acid or derivatives / Fatty acid ester / Fatty acyl

Molecular Framework

Aliphatic heteropolycyclic compounds

External Descriptors

polyketide, fatty acid ester, delta-lactone, carbobicyclic compound, statin (naturally occurring) (CHEBI:40303)

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

9LHU78OQFD

CAS number

75330-75-5

InChI Key

PCZOHLXUXFIOCF-BXMDZJJMSA-N

InChI

InChI=1S/C24H36O5/c1-5-15(3)24(27)29-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-19-12-18(25)13-22(26)28-19/h6-7,10,14-16,18-21,23,25H,5,8-9,11-13H2,1-4H3/t14-,15-,16-,18+,19+,20-,21-,23-/m0/s1

IUPAC Name

(1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate

SMILES

[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)[C@@H](C)CC

References

Synthesis Reference

Donald F. Gerson, Xinfa Xiao, "Process for the production of lovastatin using Coniothyrium fuckelii." U.S. Patent US5409820, issued January, 1984.

US5409820

General References

1. Boruta T, Bizukojc M: Production of lovastatin and itaconic acid by Aspergillus terreus: a comparative perspective. World J Microbiol Biotechnol. 2017 Feb;33(2):34. doi: 10.1007/s11274-017-2206-9. Epub 2017 Jan 19. [Article]
2. Alberts AW, Chen J, Kuron G, Hunt V, Huff J, Hoffman C, Rothrock J, Lopez M, Joshua H, Harris E, Patchett A, Monaghan R, Currie S, Stapley E, Albers-Schonberg G, Hensens O, Hirshfield J, Hoogsteen K, Liesch J, Springer J: Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3957-61. [Article]
3. Endo A: The origin of the statins. 2004. Atheroscler Suppl. 2004 Oct;5(3):125-30. doi: 10.1016/j.atherosclerosissup.2004.08.033. [Article]
4. Chiloeches A, Lasa M, Brihuega F, Montes A, Toro MJ: Effects of lovastatin on adenylyl cyclase activity and G proteins in GH4C1 cells. FEBS Lett. 1995 Mar 13;361(1):46-50. [Article]
5. Henwood JM, Heel RC: Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidaemia. Drugs. 1988 Oct;36(4):429-54. doi: 10.2165/00003495-198836040-00003. [Article]
6. Lennernas H, Fager G: Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Clin Pharmacokinet. 1997 May;32(5):403-25. doi: 10.2165/00003088-199732050-00005. [Article]
7. Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB, Klein TE: Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012 Oct;92(4):414-7. doi: 10.1038/clpt.2012.96. [Article]
8. Lamson M, Phillips G, Shen J, Lukacsko P, Friedhoff L, Niecestro RM: Pharmacokinetics of lovastatin extended-release dosage form (Lovastatin XL) in healthy volunteers. Biopharm Drug Dispos. 2002 May;23(4):143-9. doi: 10.1002/bdd.304. [Article]
9. Neuvonen PJ, Backman JT, Niemi M: Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin. Clin Pharmacokinet. 2008;47(7):463-74. doi: 10.2165/00003088-200847070-00003. [Article]
10. Greenspan MD, Yudkovitz JB, Alberts AW, Argenbright LS, Arison BH, Smith JL: Metabolism of lovastatin by rat and human liver microsomes in vitro. Drug Metab Dispos. 1988 Sep-Oct;16(5):678-82. [Article]
11. Draganov DI, Stetson PL, Watson CE, Billecke SS, La Du BN: Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem. 2000 Oct 27;275(43):33435-42. [Article]
12. Moghadasian MH: Clinical pharmacology of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Life Sci. 1999;65(13):1329-37. doi: 10.1016/s0024-3205(99)00199-x. [Article]
13. Anderson TJ, Gregoire J, Pearson GJ, Barry AR, Couture P, Dawes M, Francis GA, Genest J Jr, Grover S, Gupta M, Hegele RA, Lau DC, Leiter LA, Lonn E, Mancini GB, McPherson R, Ngui D, Poirier P, Sievenpiper JL, Stone JA, Thanassoulis G, Ward R: 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi: 10.1016/j.cjca.2016.07.510. Epub 2016 Jul 25. [Article]
14. Grundy SM, Stone NJ: 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol: Primary Prevention. JAMA Cardiol. 2019 Apr 10. pii: 2730287. doi: 10.1001/jamacardio.2019.0777. [Article]
15. Kreatsoulas C, Anand SS: The impact of social determinants on cardiovascular disease. Can J Cardiol. 2010 Aug-Sep;26 Suppl C:8C-13C. doi: 10.1016/s0828-282x(10)71075-8. [Article]
16. Kannel WB, Castelli WP, Gordon T, McNamara PM: Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med. 1971 Jan;74(1):1-12. doi: 10.7326/0003-4819-74-1-1. [Article]
17. Authors unspecified: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 Nov 5;339(19):1349-57. doi: 10.1056/NEJM199811053391902. [Article]
18. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8. [Article]
19. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207. doi: 10.1056/NEJMoa0807646. Epub 2008 Nov 9. [Article]
20. Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE: Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011 Dec 1;365(22):2078-87. doi: 10.1056/NEJMoa1110874. Epub 2011 Nov 15. [Article]
21. Authors unspecified: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):7-22. doi: 10.1016/S0140-6736(02)09327-3. [Article]
22. Authors unspecified: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994 Nov 19;344(8934):1383-9. [Article]
23. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S: Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD004816. doi: 10.1002/14651858.CD004816.pub5. [Article]
24. Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C: The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012 Aug 11;380(9841):581-90. doi: 10.1016/S0140-6736(12)60367-5. Epub 2012 May 17. [Article]
25. Adams SP, Sekhon SS, Wright JM: Lipid-lowering efficacy of rosuvastatin. Cochrane Database Syst Rev. 2014 Nov 21;(11):CD010254. doi: 10.1002/14651858.CD010254.pub2. [Article]
26. Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, Larsen ML, Bendiksen FS, Lindahl C, Szarek M, Tsai J: High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005 Nov 16;294(19):2437-45. doi: 10.1001/jama.294.19.2437. [Article]
27. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW: Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15;92(2):152-60. [Article]
28. Elsby R, Hilgendorf C, Fenner K: Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it's not just about OATP1B1. Clin Pharmacol Ther. 2012 Nov;92(5):584-98. doi: 10.1038/clpt.2012.163. Epub 2012 Oct 10. [Article]
29. Jacobsen W, Kirchner G, Hallensleben K, Mancinelli L, Deters M, Hackbarth I, Benet LZ, Sewing KF, Christians U: Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos. 1999 Feb;27(2):173-9. [Article]
30. Bradford RH, Shear CL, Chremos AN, Dujovne CA, Franklin FA, Grillo RB, Higgins J, Langendorfer A, Nash DT, Pool JL, et al.: Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. Am J Cardiol. 1994 Oct 1;74(7):667-73. doi: 10.1016/0002-9149(94)90307-7. [Article]
31. Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118. doi: 10.1146/annurev.pharmtox.45.120403.095748. [Article]
32. Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U: Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med. 2001 Jun;7(6):687-92. doi: 10.1038/89058. [Article]
33. Mahmoud AM, Aboul-Soud MA, Han J, Al-Sheikh YA, Al-Abd AM, El-Shemy HA: Transcriptional profiling of breast cancer cells in response to mevinolin: Evidence of cell cycle arrest, DNA degradation and apoptosis. Int J Oncol. 2016 May;48(5):1886-94. doi: 10.3892/ijo.2016.3418. Epub 2016 Mar 4. [Article]
34. Zhao G, Liu M, Wu X, Li G, Qiu F, Gu J, Zhao L: Effect of polymorphisms in CYP3A4, PPARA, NR1I2, NFKB1, ABCG2 and SLCO1B1 on the pharmacokinetics of lovastatin in healthy Chinese volunteers. Pharmacogenomics. 2017 Jan;18(1):65-75. doi: 10.2217/pgs.16.31. Epub 2016 Dec 14. [Article]
35. Tornio A, Vakkilainen J, Neuvonen M, Backman JT, Neuvonen PJ, Niemi M: SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid. Pharmacogenet Genomics. 2015 Aug;25(8):382-7. doi: 10.1097/FPC.0000000000000148. [Article]
36. Xiang Q, Chen SQ, Ma LY, Hu K, Zhang Z, Mu GY, Xie QF, Zhang XD, Cui YM: Association between SLCO1B1 T521C polymorphism and risk of statin-induced myopathy: a meta-analysis. Pharmacogenomics J. 2018 Dec;18(6):721-729. doi: 10.1038/s41397-018-0054-0. Epub 2018 Sep 24. [Article]
37. Lin YC, Lin JH, Chou CW, Chang YF, Yeh SH, Chen CC: Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. Cancer Res. 2008 Apr 1;68(7):2375-83. doi: 10.1158/0008-5472.CAN-07-5807. [Article]
38. Harper CR, Jacobson TA: The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Curr Opin Lipidol. 2007 Aug;18(4):401-8. doi: 10.1097/MOL.0b013e32825a6773. [Article]
39. Acton A. (2013). Advances in Lovastatin Research and Application. ScholarlyBrief.
40. Loughlin K. and Generali J. (2006). Prescription Drugs: Alternative Uses, Alternative Cures. Free Press. [ISBN:0-7432-9925-6]
41. FDA Approved Drug Products: Altoprev (lovastatin extended-release) oral tablets [Link]
42. FDA Approved Drug Products: Mevacor (lovastatin) oral tablets [Link]
43. FDA Label - Lovastatin [File]
44. Health Canada Monograph - Lovastatin [File]

External Links

Human Metabolome Database

HMDB0014372

KEGG Drug

D00359

KEGG Compound

C07074

PubChem Compound

53232

PubChem Substance

46508223

ChemSpider

48085

BindingDB

34168

RxNav

6472

ChEBI

40303

ChEMBL

CHEMBL503

ZINC

ZINC000003812841

Therapeutic Targets Database

DAP000551

PharmGKB

PA450272

Guide to Pharmacology

GtP Drug Page

PDBe Ligand

803

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Lovastatin

PDB Entries

1cqp / 7kc6

MSDS

Download (118 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Dyslipidemia / Hyperlipidemias / Mixed Hyperlipidemia	1
4	Completed	Treatment	Fragile X Syndrome / Genetic Disease	1
4	Completed	Treatment	Healthy Subjects (HS)	2
3	Completed	Prevention	Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Myocardial Ischemia	1
3	Completed	Prevention	High Cholesterol	1

Pharmacoeconomics

Manufacturers

• Andrx labs llc
• Actavis elizabeth llc
• Apotex inc
• Carlsbad technology inc
• Lupin ltd
• Mutual pharmaceutical co inc
• Mylan pharmaceuticals inc
• Sandoz inc
• Teva pharmaceuticals usa inc
• Merck research laboratories div merck co inc

Packagers

• Actavis Group
• Advanced Pharmaceutical Services Inc.
• Amerisource Health Services Corp.
• Apotex Inc.
• Apotheca Inc.
• A-S Medication Solutions LLC
• Bryant Ranch Prepack
• Cardinal Health
• Carlsbad Technology Inc.
• Comprehensive Consultant Services Inc.
• DHHS Program Support Center Supply Service Center
• Dispensing Solutions
• Diversified Healthcare Services Inc.
• Eon Labs
• Heartland Repack Services LLC
• International Laboratories Inc.
• Ivax Pharmaceuticals
• Kaiser Foundation Hospital
• Lake Erie Medical and Surgical Supply
• Lupin Pharmaceuticals Inc.
• Major Pharmaceuticals
• Mckesson Corp.
• Medvantx Inc.
• Merck & Co.
• Murfreesboro Pharmaceutical Nursing Supply
• Mutual Pharmaceutical Co.
• Mylan
• Neuman Distributors Inc.
• Nucare Pharmaceuticals Inc.
• Palmetto Pharmaceuticals Inc.
• PCA LLC
• PD-Rx Pharmaceuticals Inc.
• Pharmaceutical Utilization Management Program VA Inc.
• Pharmedix
• Physicians Total Care Inc.
• Preferred Pharmaceuticals Inc.
• Prepackage Specialists
• Prepak Systems Inc.
• Rebel Distributors Corp.
• Remedy Repack
• Resource Optimization and Innovation LLC
• Sandhills Packaging Inc.
• Sciele Pharma Inc.
• Shionogi Pharma Inc.
• Southwood Pharmaceuticals
• Teva Pharmaceutical Industries Ltd.
• UDL Laboratories
• Va Cmop Dallas
• Vangard Labs Inc.
• Watson Pharmaceuticals
• Yung Shin Pharmaceutical Industry Ltd.

Dosage Forms

Form	Route	Strength
Tablet, extended release	Oral
Tablet, extended release; tablet, multilayer, extended release	Oral
Tablet, extended release	Oral	20 mg/1
Tablet, extended release	Oral	40 mg/1
Tablet, extended release	Oral	60 mg/1
Tablet	Oral	10 MG
Tablet	Oral	10 mg/1
Tablet	Oral	20 mg/1
Tablet	Oral	40 mg/1
Tablet	Oral	40 mg
Tablet	Oral
Tablet	Oral	20 mg
Tablet	Oral	21 mg

Prices

Unit description	Cost	Unit
Altoprev 60 mg 24 Hour tablet	7.99USD	tablet
Altoprev 60 mg tablet	7.74USD	tablet
Altoprev 20 mg 24 Hour tablet	6.88USD	tablet
Altoprev 20 mg tablet	6.61USD	tablet
Mevacor 40 mg tablet	4.57USD	tablet
Altoprev 40 mg tablet	4.41USD	tablet
Lovastatin 40 mg tablet	4.36USD	tablet
Altoprev 10 mg 24 Hour tablet	3.07USD	tablet
Mevacor 20 mg tablet	2.53USD	tablet
Lovastatin 20 mg tablet	2.42USD	tablet
Altocor 20 mg 24 Hour tablet	2.36USD	tablet
Apo-Lovastatin 40 mg Tablet	2.11USD	tablet
Co Lovastatin 40 mg Tablet	2.11USD	tablet
Mylan-Lovastatin 40 mg Tablet	2.11USD	tablet
Novo-Lovastatin 40 mg Tablet	2.11USD	tablet
Pms-Lovastatin 40 mg Tablet	2.11USD	tablet
Ran-Lovastatin 40 mg Tablet	2.11USD	tablet
Ratio-Lovastatin 40 mg Tablet	2.11USD	tablet
Sandoz Lovastatin 40 mg Tablet	2.11USD	tablet
Mevacor 10 mg tablet	1.65USD	tablet
Lovastatin 10 mg tablet	1.37USD	tablet
Apo-Lovastatin 20 mg Tablet	1.14USD	tablet
Co Lovastatin 20 mg Tablet	1.14USD	tablet
Mylan-Lovastatin 20 mg Tablet	1.14USD	tablet
Novo-Lovastatin 20 mg Tablet	1.14USD	tablet
Pms-Lovastatin 20 mg Tablet	1.14USD	tablet
Ran-Lovastatin 20 mg Tablet	1.14USD	tablet
Ratio-Lovastatin 20 mg Tablet	1.14USD	tablet
Sandoz Lovastatin 20 mg Tablet	1.14USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US6080428	No	2000-06-27	2017-05-27
US6469035	No	2002-10-22	2018-03-15
US6080778	No	2000-06-27	2018-03-23
US6485748	No	2002-11-26	2017-12-12
US5916595	No	1999-06-29	2017-12-12

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	174.5 °C	'MSDS'
boiling point (°C)	559.2 ºC at 760 mmHg	Chemspider
water solubility	0.0004 mg/mL	'MSDS'
logP	4.08	'MSDS'
pKa	13.49	Chuong M. et al. (2013). International Journal of Applied Pharmaceutics.

Predicted Properties

Property	Value	Source
Water Solubility	0.0243 mg/mL	ALOGPS
logP	4.11	ALOGPS
logP	3.9	Chemaxon
logS	-4.2	ALOGPS
pKa (Strongest Acidic)	14.91	Chemaxon
pKa (Strongest Basic)	-2.8	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	3	Chemaxon
Hydrogen Donor Count	1	Chemaxon
Polar Surface Area	72.83 Å2	Chemaxon
Rotatable Bond Count	7	Chemaxon
Refractivity	113.18 m3·mol-1	Chemaxon
Polarizability	46.06 Å3	Chemaxon
Number of Rings	3	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9452
Blood Brain Barrier	+	0.9287
Caco-2 permeable	-	0.5484
P-glycoprotein substrate	Substrate	0.7861
P-glycoprotein inhibitor I	Inhibitor	0.7046
P-glycoprotein inhibitor II	Inhibitor	0.8388
Renal organic cation transporter	Non-inhibitor	0.8299
CYP450 2C9 substrate	Non-substrate	0.8333
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Substrate	0.6868
CYP450 1A2 substrate	Non-inhibitor	0.9045
CYP450 2C9 inhibitor	Non-inhibitor	0.9291
CYP450 2D6 inhibitor	Non-inhibitor	0.923
CYP450 2C19 inhibitor	Non-inhibitor	0.9026
CYP450 3A4 inhibitor	Inhibitor	0.796
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8682
Ames test	Non AMES toxic	0.8475
Carcinogenicity	Non-carcinogens	0.9519
Biodegradation	Not ready biodegradable	0.8819
Rat acute toxicity	2.0554 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.7272
hERG inhibition (predictor II)	Non-inhibitor	0.7484

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0a4r-9155000000-825da9f6a87f5a59c1c2
GC-MS Spectrum - EI-B	GC-MS	splash10-0a4i-2910000000-dc8caf3905a76d1dc259
GC-MS Spectrum - EI-B	GC-MS	splash10-0a4j-1910000000-8aeacab386a420581150
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-000i-0049000000-86650e3e374df663aa35
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-000i-0049000000-86650e3e374df663aa35
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	splash10-017j-3981000000-8a9df18d5a3d8401a040
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0k9j-0392200000-046f8ecdd9105ec8f133
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0fg2-0590000000-79f2e6dc3b230361fea3
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0092-0970000000-029f3798d63ab95ed321
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0592-0930000000-85de8f33dd78ba45de36
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-05fv-0910000000-7a730b8fcd91e3df5b8f
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-000e-0590000000-2206c97b74e146b3218d
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0092-1960000000-6b3a14df210273b89f18
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0592-1910000000-38bd634327305fe325cf
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0abd-1900000000-e7dab133ffe03d435831
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0536-2900000000-12e639483c7d1a83da05
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-002f-2900000000-ed64daa9de830f1f3cb0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0udi-0329000000-55a6c245082425bd8070
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0udi-0009300000-33ece630752546453480
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0zmi-0229100000-156afe2706f06c0f2afb
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0udi-4119100000-d84b71f541c231678af4
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0597-0694100000-afdbb9fc8669326951fa
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-000l-2957100000-418246bc2f88a9f867f3
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	216.6026803	predicted	DarkChem Lite v0.1.0
[M-H]-	205.4240803	predicted	DarkChem Lite v0.1.0
[M-H]-	211.0510803	predicted	DarkChem Lite v0.1.0
[M-H]-	206.9025803	predicted	DarkChem Lite v0.1.0
[M-H]-	211.30775	predicted	DeepCCS 1.0 (2019)
[M+H]+	218.0134803	predicted	DarkChem Lite v0.1.0
[M+H]+	206.0641803	predicted	DarkChem Lite v0.1.0
[M+H]+	211.5156803	predicted	DarkChem Lite v0.1.0
[M+H]+	205.9996803	predicted	DarkChem Lite v0.1.0
[M+H]+	213.43275	predicted	DeepCCS 1.0 (2019)
[M+Na]+	217.1368803	predicted	DarkChem Lite v0.1.0
[M+Na]+	205.8157803	predicted	DarkChem Lite v0.1.0
[M+Na]+	210.9312803	predicted	DarkChem Lite v0.1.0
[M+Na]+	206.8173803	predicted	DarkChem Lite v0.1.0
[M+Na]+	219.32207	predicted	DeepCCS 1.0 (2019)

Targets

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Binding Properties

×

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	37	N/A	N/A	A27462
IC 50 (nM)	20	N/A	N/A	A27463
IC 50 (nM)	50	N/A	N/A	A27464 / A27465
IC 50 (nM)	20100	N/A	N/A	A27466
IC 50 (nM)	19800	N/A	N/A	A27467
IC 50 (nM)	30	N/A	N/A	A27467

Details

Binding Properties1. 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Nadph binding

Specific Function

Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including...

Gene Name

HMGCR

Uniprot ID

P04035

Uniprot Name

3-hydroxy-3-methylglutaryl-coenzyme A reductase

Molecular Weight

97475.155 Da

References

1. Abe Y, Suzuki T, Ono C, Iwamoto K, Hosobuchi M, Yoshikawa H: Molecular cloning and characterization of an ML-236B (compactin) biosynthetic gene cluster in Penicillium citrinum. Mol Genet Genomics. 2002 Jul;267(5):636-46. Epub 2002 Jun 28. [Article]
2. Miyazaki A, Koieyama T, Shimada Y, Kikuchi T, Nezu H, Ito K, Kasanuki N, Koga T: Effects of pravastatin sodium on mevalonate metabolism in common marmosets. J Biochem. 2002 Sep;132(3):395-400. [Article]
3. Buxbaum JD, Geoghagen NS, Friedhoff LT: Cholesterol depletion with physiological concentrations of a statin decreases the formation of the Alzheimer amyloid Abeta peptide. J Alzheimers Dis. 2001 Apr;3(2):221-229. [Article]
4. Baranova NA, Kreier VG, Egorov NS: [Concentration on Diapak C 16 capsules of lovastatin, mevinolinic acid and other inhibitors of biosynthesis of sterins produced by Penicillium citrinum 89]. Antibiot Khimioter. 2002;47(4):3-6. [Article]
5. Farina HG, Bublik DR, Alonso DF, Gomez DE: Lovastatin alters cytoskeleton organization and inhibits experimental metastasis of mammary carcinoma cells. Clin Exp Metastasis. 2002;19(6):551-9. [Article]
6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
7. Podar K, Tai YT, Hideshima T, Vallet S, Richardson PG, Anderson KC: Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. doi: 10.1517/14728210802676278 . [Article]
8. Dimitroulakos J, Marhin WH, Tokunaga J, Irish J, Gullane P, Penn LZ, Kamel-Reid S: Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46. [Article]

Binding Properties

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Property	Measurement	pH	Temperature (°C)	References
Kd (nM)	12900	N/A	N/A	A27461

Details

Binding Properties2. Integrin alpha-L

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

General Function

Metal ion binding

Specific Function

Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated ...

Gene Name

ITGAL

Uniprot ID

P20701

Uniprot Name

Integrin alpha-L

Molecular Weight

128768.495 Da

References

1. Kallen J, Welzenbach K, Ramage P, Geyl D, Kriwacki R, Legge G, Cottens S, Weitz-Schmidt G, Hommel U: Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. J Mol Biol. 1999 Sep 10;292(1):1-9. [Article]
2. Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U: Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med. 2001 Jun;7(6):687-92. doi: 10.1038/89058. [Article]
3. Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118. doi: 10.1146/annurev.pharmtox.45.120403.095748. [Article]

Binding Properties

×

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	25933	N/A	N/A	A27467

Details

Binding Properties3. Histone deacetylase 2

Kind

Protein

Organism

Humans

Pharmacological action

No

Actions

Inhibitor

General Function

Transcription factor binding

Specific Function

Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...

Gene Name

HDAC2

Uniprot ID

Q92769

Uniprot Name

Histone deacetylase 2

Molecular Weight

55363.855 Da

References

1. Lin YC, Lin JH, Chou CW, Chang YF, Yeh SH, Chen CC: Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. Cancer Res. 2008 Apr 1;68(7):2375-83. doi: 10.1158/0008-5472.CAN-07-5807. [Article]
2. Zhang L, Kang W, Lu X, Ma S, Dong L, Zou B: Weighted gene co-expression network analysis and connectivity map identifies lovastatin as a treatment option of gastric cancer by inhibiting HDAC2. Gene. 2019 Jan 10;681:15-25. doi: 10.1016/j.gene.2018.09.040. Epub 2018 Sep 25. [Article]
3. Luthje P, Walker S, Kamolvit W, Mohanty S, Putsep K, Brauner A: Statins influence epithelial expression of the anti-microbial peptide LL-37/hCAP-18 independently of the mevalonate pathway. Clin Exp Immunol. 2019 Feb;195(2):265-276. doi: 10.1111/cei.13217. Epub 2018 Oct 11. [Article]

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Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55