LOVASTATIN

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Trade Names
Synonyms
Status
Molecule Category UNKNOWN
ATC C10AA02
UNII 9LHU78OQFD
EPA CompTox DTXSID5020784

Structure

InChI Key PCZOHLXUXFIOCF-BXMDZJJMSA-N
Smiles CC[C@H](C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(=O)O3)[C@H]21
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

Physicochemical Descriptors

Property Name Value
Molecular Formula C24H36O5
Molecular Weight 404.55
AlogP 4.2
Hydrogen Bond Acceptor 5.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 6.0
Polar Surface Area 72.83
Molecular species NEUTRAL
Aromatic Rings 0.0
Heavy Atoms 29.0

Metabolites Network

visNetwork

Bioactivity

Mechanism of Action Action Reference
HMG-CoA reductase inhibitor INHIBITOR DailyMed
Protein: HMG-CoA reductase
Description: 3-hydroxy-3-methylglutaryl-coenzyme A reductase
Organism : Homo sapiens
P04035 ENSG00000113161
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Adhesion
- 2400 12900 - 38-61
Enzyme Hydrolase
- - - 1100-5012 -
Enzyme Oxidoreductase
- 3-530 - 1 -90-84
Enzyme
- 3-530 - 1100-5012 -90-84
Epigenetic regulator Eraser Histone deacetylase HDAC class I
- 11911 - - -
Epigenetic regulator Eraser Histone deacetylase HDAC class IIb
- 16285 - - -
Membrane receptor
- 2400 12900 - -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC21/SLCO family of organic anion transporting polypeptides
- - - - 21-101
Transporter Primary active transporter ATP-binding cassette ABCB subfamily
- 19300-19300 - - -
Assay Description Organism Bioactivity Reference
Inhibitory activity against partially purified rat liver HMG-CoA reductase in vitro; 0.23-0.71 None 400.0 nM
Inhibition of microsomal rat liver HMG-CoA reductase None 11.0 nM
Tested for inhibition of rat liver microsomal HMG-CoA reductase None 7.0 nM
Tested in vitro for the HMG-CoA reductase inhibitory activity in a microsomal preparation None 530.0 nM
In vitro inhibitory activity against isolated enzyme HMG-CoA reductase None 27.0 nM
Inhibition of the incorporation of sodium [14C]acetate into cholesterol in HEP G2 cells. None 50.0 nM
Tested for ability to inhibit incorporation of [14C]acetate into cholesterol in cultured human hepatoma (HEP-G2) cells; 0.061-0.10 Homo sapiens 79.0 nM
Concentration required to inhibit HMG-CoA reductase by 50% was determined in HES 9 cell line Homo sapiens 13.0 nM
Tested in vitro for the inhibition of HMG-CoA reductase from partially purified microsomal preparations. Canis lupus familiaris 20.0 nM
Compound was evaluated for inhibitory activity against HMG-CoA reductase in HepG2 cells None 39.0 nM
Concentration required to inhibit HMG-CoA reductase by 50% was determined in Hep G2 cell line None 37.0 nM
Inhibition of cellular HMG-CoA reductase in cultures of hepatic cells (HEP G2, a human hepatoma cell line) None 0.05 nM
Inhibition of cellular HMG-CoA reductase in cultures of human HEP G2 cells, determined by decreased incorporation of sodium [14C]acetate into cholesterol. None 50.0 nM
Compound was evaluated for inhibitory activity against HMG-CoA reductase from rat hepatocyte None 32.0 nM
Compound was evaluated for the inhibition of HMG-CoA reductase (COR) in rats. None 28.0 nM
In vitro inhibition of HMG-CoA reductase in solubilized rat liver. None 8.0 nM
In vitro inhibition of HMG-CoA reductase of rat liver None 8.0 nM
Inhibition of rat liver microsomal HMG-CoA reductase Rattus norvegicus 3.0 nM
In vitro inhibition of rat liver HMG-CoA reductase None 8.0 nM
In vitro inhibitory activity was measured against rat liver HMG-CoA reductase None 27.0 nM
In vitro inhibitory activity was measured against rat liver HMG-CoA reductase using [2-14C]-acetate incorporation None 32.0 nM
Tested for inhibition of cholesterol biosynthesis in HEP G2 cells Homo sapiens 29.0 nM
Compound was tested for its Cholesterol Synthesis Inhibition ability in rats. Rattus norvegicus 25.0 nM
Compound was evaluated for the percentage of acute inhibition of cholesterol synthesis (AICS) in male rats through peroral rout. Rattus norvegicus 72.0 %
Inhibition of hepatic cholesterol de novo synthesis in male rats after po administration, Rattus norvegicus 14.0 %
The compound was tested in vivo for the inhibition of cholesterol biosynthesis in chow-fed rats at 1.0 mg/kg. Rattus norvegicus 64.0 %
Inhibition of v-ras posttranslational processing in NIH3T3 cells at 15 uM Mus musculus 90.0 %
Inhibition of human HMGCoA reductase Homo sapiens 0.6 nM Inhibition of human HMGCoA reductase Homo sapiens 2.0 nM
Inhibition of sICAM1/LFA1 interaction-mediated human THP1 cell adhesion after 1 hr by ELISA Homo sapiens 8.0 ug.mL-1
Inhibition of sICAM1/LFA1 interaction-mediated human THP1 cell adhesion at 12.50 ug/mL after 1 hr by ELISA Homo sapiens 61.4 %
Inhibition of sICAM1/LFA1 interaction-mediated human THP1 cell adhesion at 6.25 ug/mL after 1 hr by ELISA Homo sapiens 37.7 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 1 uM by spectrophotometry in presence of NADPH None -26.98 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 5 uM by spectrophotometry in presence of NADPH None -36.18 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 10 uM by spectrophotometry in presence of NADPH None -48.74 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 20 uM by spectrophotometry in presence of NADPH None -65.32 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 50 uM by spectrophotometry in presence of NADPH None -80.65 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 100 uM by spectrophotometry in presence of NADPH None -89.97 %
DRUGMATRIX: HMG-CoA Reductase enzyme inhibition (substrate: [14C]HMG-CoA) Escherichia coli 20.0 nM
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 5 uM None 27.5 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 10 uM None 46.7 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 25 uM None 69.1 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 50 uM None 77.3 %
Inhibition of HMG-CoA reductase using HMG-CoA as substrate at 100 uM None 84.4 %
TP_TRANSPORTER: inhibition of Digoxin transepithelial transport (basal to apical) (Digoxin: 5 uM, Lovastatin: 100 uM) in Caco-2 cells None 65.0 %
TP_TRANSPORTER: inhibition of Fexofenadine uptake (Fexofenadine: 2 uM, Lovastatin: 100 uM) in Xenopus laevis oocytes Xenopus laevis 95.0 %
Inhibition of human liver OATP1B1 expressed in HEK293 Flp-In cells assessed as reduction in E17-betaG uptake at 20 uM by scintillation counting Homo sapiens 66.5 %
Inhibition of human liver OATP1B3 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E17-betaG uptake at 20 uM incubated for 5 mins by scintillation counting Homo sapiens 21.3 %
Inhibition of human liver OATP2B1 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E3S uptake at 20 uM incubated for 5 mins by scintillation counting Homo sapiens -17.9 %
Inhibition of HMGR isolated from Mus musculus (mouse) liver assessed as change in NADPH at 8 umol/l by HPLC analysis Mus musculus 20.2 %
Inhibition of recombinant HMG-CoA reductase (unknown origin) after 10 mins by spectrophotometric analysis Homo sapiens 29.5 nM
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM Cricetulus griseus 87.54 %
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM Cricetulus griseus 100.71 %
Reductase Activity Assay: The HMGR activity was performed using HMG-CoA reductase assay kit from Sigma-Aldrich with the human recombinant protein or 100 μg total cell lysates from A549 cells. Lovastatin was used as a positive control, and SAHA as a negative control. HMGR activity under defined assay conditions, containing NADPH and HMG-CoA substrate in a final volume of 0.2 mL of 100 mM potassium phosphatate buffer (120 mM KCI, 1 mM EDTA, 5 mM DTT, pH 7.4), were initiated in the presence or absence (control) of test compounds dissolved in dimethylsulfoxide (DMSO). The rates of NADPH consumption were monitored every 20 seconds, for up to 10 minutes, by spectrophotometer at 37° C. and 340 nm. None 29.5 nM
Inhibition of human HMGR catalytic domain at 200 uM using HMG-CoA as substrate measured every 20 secs for 10 mins relative to control Homo sapiens 42.0 %
Reductase Activity Assay: The HMGR activity was performed using HMG-CoA reductase assay kit from Sigma-Aldrich with the human recombinant protein or 100 μg total cell lysates from A549 cells. Lovastatin was used as a positive control, and SAHA as a negative control. HMGR activity under defined assay conditions, containing NADPH and HMG-CoA substrate in a final volume of 0.2 mL of 100 mM potassium phosphatate buffer (120 mM KCl, 1 mM EDTA, 5 mM DTT, pH 7.4), were initiated in the presence or absence (control) of test compounds dissolved in dimethylsulfoxide (DMSO). The rates of NADPH consumption were monitored every 20 seconds, for up to 10 minutes, by spectrophotometer at 37° C. and 340 nm. None 29.5 nM
Inhibition of HMG-CoA reductase (unknown origin) using [14C]-HMG-CoA as substrate after 5 mins in presence of NADPH Homo sapiens 2.2 nM
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600) Staphylococcus aureus subsp. aureus 9.76 %
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600) Escherichia coli 0.96 %
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600) Klebsiella pneumoniae 12.43 %
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600) Pseudomonas aeruginosa 18.99 %
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600 Acinetobacter baumannii 19.83 %
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630 Candida albicans 17.1 %
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570) Cryptococcus neoformans -5.68 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 19.66 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 6.32 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 5.696 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.61 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.65 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.65 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.61 %

Related Entries

Cross References

Resources Reference
ChEBI 40303
ChEMBL CHEMBL503
DrugBank DB00227
DrugCentral 1612
FDA SRS 9LHU78OQFD
Human Metabolome Database HMDB0014372
Guide to Pharmacology 2739
KEGG C07074
PDB 803
PharmGKB PA450272
PubChem 53232
SureChEMBL SCHEMBL3136
ZINC ZINC000003812841
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