SIMVASTATIN

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Trade Names
Synonyms
Status
Molecule Category Free-form
ATC C10AA01
UNII AGG2FN16EV
EPA CompTox DTXSID0023581

Structure

InChI Key RYMZZMVNJRMUDD-HGQWONQESA-N
Smiles CCC(C)(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/C25H38O5/c1-6-25(4,5)24(28)30-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-19-13-18(26)14-22(27)29-19/h7-8,11,15-16,18-21,23,26H,6,9-10,12-14H2,1-5H3/t15-,16-,18+,19+,20-,21-,23-/m0/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C25H38O5
Molecular Weight 418.57
AlogP 4.59
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 30.0

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(%)
Enzyme Cytochrome P450 Cytochrome P450 family 2 Cytochrome P450 family 2C Cytochrome P450 2C8
- 3700 - - -
Enzyme Hydrolase
- - - 750-5012 -
Enzyme Oxidoreductase
- 1-6110 - 3-68000 -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC21/SLCO family of organic anion transporting polypeptides
- 4400-11000 - - 29-60
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC22 family of organic cation and anion transporters
- - - - 23
Transporter Primary active transporter ATP-binding cassette ABCB subfamily
- 24700-24700 - - -
Assay Description Organism Bioactivity Reference
In vitro inhibitory activity was evaluated on cholesterol biosynthesis in HepG2 cells Homo sapiens 40.0 nM
Inhibitory constant against HMG-CoA reductase Homo sapiens 2.6 nM
Inhibitory concentration against HMG-CoA reductase Homo sapiens 11.2 nM
Inhibitory concentration against 3-hydroxy-3-methylglutaryl-CoA reductase Homo sapiens 11.0 nM
Inhibition of HMGCoA reductase None 49.0 nM
Inhibition of cholesterol synthesis in rat hepatocytes Rattus norvegicus 4.0 nM
Inhibition of cholesterol synthesis in mouse at 1 mg/kg Mus musculus -45.0 %
Inhibition of rat microsomal HMG-CoA reductase assessed as inhibition of cholesterol synthesis after 30 mins Rattus norvegicus 18.0 nM
Inhibition of cholesterol synthesis in rat liver hepatocytes after 4 hrs Rattus norvegicus 1.3 nM
Inhibition of cholesterol synthesis in rat L6 cells after 3 hrs Rattus norvegicus 229.0 nM
Inhibition of cholesterol synthesis in C57/BL6 mouse at 30 mg/kg, po by MAICS assay Mus musculus -44.0 %
Inhibition of HMG-CoA reductase None 49.0 nM
Inhibition of cholesterol synthesis in rat hepatocyte Rattus norvegicus 1.3 nM
Inhibition of cholesterol synthesis in rat myocyte Rattus norvegicus 150.0 nM
Inhibition of acute cholesterol synthesis in mouse at 1 mg/kg Mus musculus -45.0 %
Inhibition of cholesterol synthesis in rat hepatocyte Rattus norvegicus 1.3 nM
Inhibition of cholesterol synthesis in rat L6 myocyte Rattus norvegicus 150.0 nM
Inhibition of HMGR in rat hepatic microsomes assessed as conversion of [14C]HMG-CoA to [14C]mevalonic acid Rattus norvegicus 4.3 nM
Inhibition of cholesterol synthesis in rat hepatocytes assessed as incorporation of [14C]acetate into cholesterol Rattus norvegicus 6.2 nM
Inhibition of cholesterol synthesis in rat L6 cells assessed as incorporation of [14C]acetate into cholesterol Rattus norvegicus 27.0 nM
Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells at 100 uM by confocal microscopy Homo sapiens 22.6 %
DRUGMATRIX: HMG-CoA Reductase enzyme inhibition (substrate: [14C]HMG-CoA) Escherichia coli 3.39 nM
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 73.1 %
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 29.3 %
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 47.4 %
Inhibition of Equus caballus (horse) serum butyrylcholinesterase (BChE) assessed as inhibition of BTCh hydrolysis by Ellman method Equus caballus 750.0 nM
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM Cricetulus griseus 44.72 %
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM Cricetulus griseus 60.18 %
In vivo antidyslipidemic activity against Triton WR 1339-induced hyperlipidemic Wistar rat model assessed as decrease in total cholesterol level in plasma at 56 umol/kg, ip administered as single dose 1 hr after Triton WR 1339 challenge measured after 24 hrs Rattus norvegicus 75.0 %
In vivo antidyslipidemic activity against Triton WR 1339-induced hyperlipidemic Wistar rat model assessed as decrease in LDL-cholesterol level in plasma at 56 umol/kg, ip administered as single dose 1 hr after Triton WR 1339 challenge measured after 24 hrs Rattus norvegicus 70.0 %
In vivo antidyslipidemic activity against Triton WR 1339-induced hyperlipidemic Wistar rat model assessed as decrease in triglyceride level in plasma at 56 umol/kg, ip administered as single dose 1 hr after Triton WR 1339 challenge measured after 24 hrs Rattus norvegicus 0.0 %
Inhibition of human HMG-CoA reductase after 30 mins Homo sapiens 39.81 nM
Antihyperlipidemic activity in Triton WR1339-induced hyperlipidemic rat assessed as reduction in plasma total cholesterol at 56 umol/kg, ip dosed 1 hr after Triton WR1339 challenge and measured 24 hrs post dose relative to control Rattus norvegicus 75.0 %
Antihypercholesterolemic activity in Triton WR1339-induced hyperlipidemic rat assessed as reduction in plasma LDL-C level at 56 umol/kg, ip dosed 1 hr after Triton WR1339 challenge and measured 24 hrs post dose relative to control Rattus norvegicus 70.0 %
Antihyperlipidemic activity in Triton WR1339-induced hyperlipidemic rat assessed as reduction in plasma triglyceride level at 56 umol/kg, ip dosed 1 hr after Triton WR1339 challenge and measured 24 hrs post dose relative to control Rattus norvegicus 0.0 %
Induction of mitochondrial dysfunction in Sprague-Dawley rat liver mitochondria assessed as inhibition of mitochondrial respiration per mg mitochondrial protein measured for 20 mins by A65N-1 oxygen probe based fluorescence assay Rattus norvegicus 100.0 nM
Inhibition of HMG-CoA reductase (unknown origin) using [14C]-HMG-CoA as substrate after 5 mins in presence of NADPH Homo sapiens 0.9 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 -19.3 %
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600) Escherichia coli 6.01 %
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600) Klebsiella pneumoniae -2.13 %
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600) Pseudomonas aeruginosa 2.51 %
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600 Acinetobacter baumannii 12.35 %
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630 Candida albicans 14.81 %
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 3.41 %
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 6.61 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 7.21 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 5.251 %
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 0.43 % 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 0.5 % 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 0.5 % 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 0.43 %

Related Entries

Cross References

Resources Reference
ChEBI 9150
ChEMBL CHEMBL1064
DrugBank DB00641
DrugCentral 2445
FDA SRS AGG2FN16EV
Human Metabolome Database HMDB0005007
Guide to Pharmacology 2955
PharmGKB PA451363
PubChem 54454
SureChEMBL SCHEMBL2471
ZINC ZINC000003780893
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