General
Preferred name
ATORVASTATIN
Synonyms
ATORVASTATIN CALCIUM ()
Atorvastatin hemicalcium salt ()
Lipitor ()
Atorvastatin Calcium Trihydrate ()
Atorvastatin (sodium) ()
Atorvastatin (hemicalcium salt) ()
CI-981 ()
Atorvastatin hemicalcium ()
Atorvastatin Sodium ()
Atorvastatin (calcium salt hydrate) ()
Atorvastatin-d5 (calcium salt) ()
Atorvastatin calcium component of caduet ()
Atorvastatin calcium component of ocustatin trihydrate ()
Atorvastatin calcium anhydrous ()
Torvast ()
Atorvastatin calcium salt anhydrous ()
Totalip ()
Atorvastatin calcium trihydrate ()
NSC-758617 ()
Atorvastatin calcium salt trihydrate ()
Atorvastatin calcium component of liptruzet ()
Atorvaliq ()
Atorvastatin calcium hydrate ()
Atorvastatin calcium (anhydrous) ()
Atorvastatina ()
Prevencor ()
Atorvastatine ()
Sortis ()
Tahor ()
Zarator ()
Cardyl ()
P&D ID
PD013106
CAS
134523-03-8
134523-00-5
110862-48-1
344423-98-9
134523-01-6
357164-38-6
222412-82-0
Tags
available
probe
prodrug
drug
Approved by
FDA
First approval
1996
Drug indication
Coronavirus Disease 2019 (COVID-19)
Cardiovascular disease
Combined hyperlipidemia
Drug Status
approved
Max Phase
4.0
Probe info
Probe type
calculated probe
experimental probe
P&D approved
Probe selectivity
protein-selective
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Probe control not defined
Orthogonal probes
4
No orthogonal probes found
Similar probes
1
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Atorvastatin's effects lower the amount of low-density lipoprotein (LDL) cholesterol,[A177388] total cholesterol, apolipoprotein B, very low-density lipoprotein cholesterol and triglycerides while increasing the secretion of high-density lipoprotein cholesterol. In patients presenting dysbetalipoproteinemia, atorvastatin has been shown to also reduce the intermediate-density lipoprotein cholesterol.[A177397]; ; The partial depletion of cellular cholesterol is known to lead to an increased expression of LDL receptors on hepatocytes which in order increased the LDL uptake by the hepatocytes and a driven decrease of this cholesterol type in the blood.[A177415]; ; In clinical trials, the effects of atorvastatin towards total cholesterol, LDL and triglycerides were shown to be dose-dependent and to present an effect ranging from 36-53% decrease in the level of LDL cholesterol.[A177415]; ; As a preventive therapy, the administration of atorvastatin in hypertensive patients presented 36% less nonfatal myocardial infarctions and fatal coronary artery disease. As well, in type 2 diabetes patients, atorvastatin was shown to reduce the risk of cardiovascular disease in 37% of the patients.[A177415]; ; It has been suggested that atorvastatin can reduce angiogenesis which can be useful in conditions of chronic subdural hematoma.[A177388]
HALF-LIFE
The half-life of atorvastatin is of about 14 hours while the half-life of its metabolites can reach up to 30 hours.[A177397]
ROE
Atorvastatin is mainly eliminated in the bile without enterohepatic recirculation.[A177397] The renal elimination of atorvastatin is very minimal and represents less than 1% of the eliminated dose.[A19474]
INDICATION
Atorvastatin is approved for the treatment of several types of dyslipidemias including:; ; - Primary hyperlipidemia and mixed dyslipidemia in adults.; - Hypertriglyceridemia.; - Primary dysbetalipoproteinemia.; - Homozygous familial hypercholesterolemia.; - Heterozygous familial hypercholesterolemia in adolescent patients with failed dietary modifications.[A177397]; ; Dyslipidemia is defined as an elevation of plasma cholesterol, triglycerides or both as well as to the presence of low levels of high-density lipoprotein. This condition represents an increased risk for the development of atherosclerosis.[L6025] ; ; Atorvastatin is indicated, in combination with dietary modifications, to prevent cardiovascular events in patients with cardiac risk factors and/or abnormal lipid profiles.[A177397]; ; Atorvastatin can be used as a preventive agent for myocardial infarction, stroke, revascularization, and angina, in patients without coronary heart disease but with multiple risk factors, and in patients with type 2 diabetes without coronary heart disease but multiple risk factors.[A177397]; ; Atorvastatin can also be used as a preventive agent for non-fatal myocardial infarction, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure and angina in patients with coronary heart disease.[A177397]; ; The term cardiovascular events correspond to all the incidents that can produce damage to the heart muscle including the interruption of blood flow.[L6028]
TOXICITY
The reported LD50 of oral atorvastatin in mice is higher than 5000 mg/kg.[MSDS] In cases of overdose with atorvastatin, there is reported symptoms of complicated breathing, jaundice, liver damage, dark urine, muscle pain, and seizures.[L6031] In case of overdose, symptomatic treatment is recommended and due to the high plasma protein binding, hemodialysis is not expected to generate significant improvement.[FDA label]; ; In carcinogenic studies with high doses of atorvastatin, evidence of rhabdomyosarcoma, fibrosarcoma, liver adenoma, and liver carcinoma were observed.[FDA label]; ; In fertility studies with high doses of atorvastatin, there were events of aplasia, aspermia, low testis and epididymal weight, decreased sperm motility, decreased spermatid head concentration and increased abnormal sperm.[FDA label]; ; Atorvastatin was shown to not be mutagenic in diverse mutagenic assays.[FDA label]
ABSORPTION
Atorvastatin presents a dose-dependent and non-linear pharmacokinetic profile.[A177436] It is very rapidly absorbed after oral administration. After the administration of a dose of 40 mg, its peak plasma concentration of 28 ng/ml is reached 1-2 hours after initial administration with an AUC of about 200 ng.h/ml.[A177478] It does present a very large first-pass metabolism and hence, its bioavailability is of only 14%.[A177397]; ; Administration of atorvastatin with food results in prolonged Tmax and a reduction in Cmax and AUC.[A177415]
DESCRIPTION
The 3S, 5S-Atorvastatin enantiomer is inactive . Atorvastatin is metabolised to form active metabolites atorvastatin lactone (CID 6483036), o-hydroxyatorvastatin (CID 9808225) and p-hydroxyatorvastatin (CID 9851106).
Atorvastatin calcium is found in combination with amlodipine besylate in the drug Caduet®. (GtoPdb)
Atorvastatin calcium is found in combination with amlodipine besylate in the drug Caduet®. (GtoPdb)
MOA
Atorvastatin is a reversible competitor of the 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA).[A177388] It acts by binding to the critical catalytic site of the enzyme.[T568] The HMG-CoA reductase is an enzyme that catalyzes the reduction of HMG-CoA to mevalonate which is a rate-limiting step in the cholesterol synthesis in the liver.[A177415] Hence, the blockade of this enzyme later reduces _de novo_ cholesterol production.[A177397]; ; As part of atorvastatin's effects, it has been observed an increase in the number of LDL receptors on the surface of the hepatic cells.[A177397] As well, as atorvastatin presents a reduction on cholesterol levels which are required for the secretion of very-low-density lipoprotein; hence, the secretion and formation of this cholesterol isotype is significantly reduced which in order reduces the level of circulating triglycerides.[A177436]; ; The mechanism of the increase in the level of high-density lipoprotein cholesterol is still unknown.[A177436]
METABOLISM
Atorvastatin is highly metabolized in the bile followed by the liver and extra-hepatically metabolism.[A177436] The metabolism is performed mainly by the activity of cytochrome P450 3A4 and its metabolic pathway produces mainly active ortho- and para-hydroxylated metabolites[A177397] as well as various beta-oxidation minor metabolites.[A177415] The metabolism of atorvastatin is ruled by reactions of oxidation, lactonization and glucuronidation.[A19474]; ; The ortho- and para-hydroxylated metabolites of atorvastatin account for about 70% of the activity against HMG-CoA reductase.[A177415] After the generation of this major metabolites, they are processed via glucuronidation driven by the enzymes UGT1A1 and UGT1A3.[A19474]
DESCRIPTION
Atorvastatin is an orally active HMG-CoA reductase inhibitor, has the ability to effectively decrease blood lipids. Atorvastatin inhibits human SV-SMC proliferation and invasion with IC50s of 0.39 ¦ÌM and 2.39 ¦ÌM, respectively[1][2][3].
PRICE
46
DESCRIPTION
Atorvastatin, an orally active HMG-CoA reductase inhibitor, effectively lowers blood lipids by activating liver cytochrome p450 to accelerate metabolism. Atorvastatin inhibits the proliferation and invasion of human SV-SMC cells with IC50 values of 0.39 ??M and 2.39 ??M, respectively. [Atorvastatin] combined with clopidogrel may lead to increased thrombotic events in patients.
DESCRIPTION
Atorvastatin hemicalcium salt (CI-981) is an orally active 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has the ability to effectively decrease blood lipids. Atorvastatin hemicalcium salt inhibits human SV-SMC proliferation and invasion with IC50s of 0.39 ¦ÌM and 2.39 ¦ÌM, respectively[1][2][3].
PRICE
53
MOA
Inhibitor, Prodrug
(Chemical Probes.org)
DESCRIPTION
Potent HMG-CoA reductase inhibitor
(Tocriscreen Plus)
DESCRIPTION
Atorvastatin, an orally active HMG-CoA reductase inhibitor, effectively lowers blood lipids by activating liver cytochrome p450 to accelerate metabolism. Atorvastatin inhibits the proliferation and invasion of human SV-SMC cells with IC50 values of 0.39 μM and 2.39 μM, respectively. [Atorvastatin] combined with clopidogrel may lead to increased thrombotic events in patients.
(TargetMol Bioactive Compound Library)
DESCRIPTION
Atorvastatin is an HMG-CoA reductase inhibitor used to lower lipid levels and reduce the risk of cardiovascular disease including myocardial infarction and stroke.
(Enamine Bioactive Compounds)
DESCRIPTION
Atorvastatin Sodium (Lipitor) is a competitive inhibitor of HMG-CoA reductase and increases the expression of low density lipoprotein (LDL) receptors on hepatocytes. Atorvastatin Sodium treatment inhibits aquaporin 4 to reduce ischaemic brain oedema.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
8
Organisms
2
Compound Sets
38
Axon Medchem Screening Library
ChEMBL Approved Drugs
ChEMBL Drugs
Chemical Probes.org
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP Approved Drugs
Enamine Bioactive Compounds
Enamine BioReference Compounds
Guide to Pharmacology
High-quality chemical probes
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Other bioactive compounds
Prestwick Chemical Library
Probe Miner (suitable probes)
ReFrame library
Selleckchem Bioactive Compound Library
The Spectrum Collection
Tocriscreen Plus
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
109
Molecular Weight
558.25
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
4
Rotatable Bonds
12
Ring Count
4
Aromatic Ring Count
4
cLogP
6.31
TPSA
111.79
Fraction CSP3
0.27
Chiral centers
2.0
Largest ring
6.0
QED
0.16
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Enzymes
Target
HMG-CoA Reductase (HMGCR)
LDL
Aquaporin
AHR, DPP4, HMGCR
HMG-CoA inhibitor
Ferroptosis
Apoptosis related,Autophagy,HMG-CoA Reductase
Autophagy,HMG-CoA Reductase
HMGCR
HMG-CoA Reductase
Member status
member
MOA
HMG-CoA Reductase Inhibitors
HMGCR inhibitor
Indication
stroke, heart attack
Disease Area
neurology/psychiatry, cardiology
Pathway
Autophagy
Metabolism
Membrane Transporter/Ion Channel
Metabolic Enzyme/Protease
Apoptosis
Biosynthetic Origin
Polyketide
Therapeutic Indication
Hypocholesterolemic
Therapeutic Class
Cardiovascular
Anticholesteremic Agents
Antiviral Agents
Target class
Lipid metabolism
Target subclass
Sterol biosynthesis
Control
3S, 5S-Atorvastatin
Source data
