Drug Details

General Information of the Drug (ID: DR2980)
Name
Simvastatin
Synonyms
simvastatin; 79902-63-9; Zocor; Synvinolin; Sinvacor; Denan; Lipex; MK-733; Sivastin; Lodales; Simvastatine; Cholestat; Colemin; Simovil; Medipo; Pantok; Simvastatina; Simvastatinum; Velostatin; Zocord; Zorced; Simvastatin lactone; Simvastatin (Zocor); Lipovas; Simcard; Simvacor; Simvoget; Rechol; Simlup; (1S,3R,7S,8S,8aR)-8-(2-((2R,4R)-4-Hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate; MK-0733; UNII-AGG2FN16EV; 2,2-Dimethylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one; AGG2FN16EV; CHEBI:9150; (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate; [(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] 2,2-dimethylbutanoate; Labistatin; Coledis; Corolin; Nivelipol; Rendapid; Vasotenal; Simcor; Simvastatin, 98%; Butanoic acid, 2,2-dimethyl-, (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 ester; C25H38O5; Simvastatine [French]; Simvastatinum [Latin]; Simvastatina [Spanish]; DSSTox_CID_3581; DSSTox_RID_77090; DSSTox_GSID_23581; (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 2,2-dimethylbutanoate; Butanoic acid, 2,2-dimethyl-, (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 ester; Zosta; Simvast CR; DRG-0320; [(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxo-tetrahydropyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate; SMR000718785; MK 0733; CCRIS 7558; Zocor (TN); HSDB 7208; Simvastatin & Primycin; SR-05000001894; MK 733; L 644128-000U; BRN 4768037; Kolestevan; Lipinorm; Modutrol; Simvotin; Sinvascor; Valemia; Eucor; MFCD00072007; Nor-Vastina; Simvastatin,(S); C10AA01; simvastatin predrug; (+)-Simvastatin; NCGC00016940-01; inactive simvastatin; 8-[2-((2R,4R)-4-hydroxy-6-oxo(2H-3,4,5-trihydropyran-2-yl))ethyl](1S,7S,8S,3R, 8aR)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthyl 2,2-dimethylbutanoate; Simvastatin [USAN:USP:INN:BAN]; TNP00259; Prestwick_171; CAS-79902-63-9; KS-1113; Spectrum_001717; SpecPlus_000895; Prestwick0_000865; Prestwick1_000865; Prestwick2_000865; Prestwick3_000865; Spectrum2_001671; Spectrum3_000669; Spectrum4_000632; Spectrum5_001428; SCHEMBL2471; CHEMBL1064; BSPBio_000909; BSPBio_002337; KBioGR_001244; KBioSS_002197; MLS001304029; MLS001333077; MLS001333078; MLS002154038; MLS006011866; ARONIS24119; BIDD:GT0769; DivK1c_006991; SPECTRUM1504236; SPBio_001881; SPBio_002830; BPBio1_001001; GTPL2955; Simvastatin (JP17/USP/INN); Simvastatin, analytical standard; DTXSID0023581; BCBcMAP01_000007; KBio1_001935; KBio2_002197; KBio2_004765; KBio2_007333; KBio3_001557; RYMZZMVNJRMUDD-HGQWONQESA-; HMS1570N11; HMS1922H13; HMS2089D12; HMS2093E06; HMS2097N11; HMS2231N22; HMS3259B12; HMS3412P08; HMS3676P08; HMS3714N11; HMS3884G10; Pharmakon1600-01504236; ZINC3780893; Tox21_110696; Tox21_300400; BBL024390; BDBM50139181; CCG-39069; NSC633782; NSC758706; s1792; SBB080618; STK801938; AKOS005111006; AKOS015842733; Simvastatin, >=97% (HPLC), solid; Tox21_110696_1; AC-1530; AT-7048; DB00641; MCULE-8390617062; NC00719; NSC 758706; NSC-633782; NSC-758706; MRF-0000729; NCGC00017324-01; NCGC00017324-02; NCGC00017324-03; NCGC00017324-04; NCGC00017324-05; NCGC00017324-07; NCGC00017324-08; NCGC00017324-09; NCGC00254418-01; 2,2-Dimethylbutanoic acid (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 ester; Butanoic acid, 2,2-dimethyl-, 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester, (1S-(1alpha,3alpha,7beta,8beta(2S*,4S*),8abeta))-; HY-17502; ST057168; SBI-0206773.P001; Simvastatin 100 microg/mL in Acetonitrile; AB0069097; D00434; J10128; W-3044; 28049-EP2269989A1; 28049-EP2269990A1; 28049-EP2270011A1; 28049-EP2270505A1; 28049-EP2272825A2; 28049-EP2272841A1; 28049-EP2277865A1; 28049-EP2280001A1; 28049-EP2280006A1; 28049-EP2281813A1; 28049-EP2284158A1; 28049-EP2287165A2; 28049-EP2287166A2; 28049-EP2292620A2; 28049-EP2295406A1; 28049-EP2295409A1; 28049-EP2295417A1; 28049-EP2295422A2; 28049-EP2298731A1; 28049-EP2298742A1; 28049-EP2298745A1; 28049-EP2298769A1; 28049-EP2298772A1; 28049-EP2298776A1; 28049-EP2298779A1; 28049-EP2301923A1; 28049-EP2301931A1; 28049-EP2301936A1; 28049-EP2305219A1; 28049-EP2305648A1; 28049-EP2308839A1; 28049-EP2308878A2; 28049-EP2314588A1; 96639-EP2287163A1; 96639-EP2305678A1; 99548-EP2270011A1; 99548-EP2298779A1; 99548-EP2301923A1; 99548-EP2301931A1; AB00053395-07; AB00053395-08; AB00053395-10; AB00053395_11; AB00053395_13; 902S639; Q670131; SR-05000001894-1; SR-05000001894-2; BRD-K22134346-001-05-8; BRD-K22134346-001-11-6; BRD-K22134346-001-15-7; Z1741982918; Simvastatin, British Pharmacopoeia (BP) Reference Standard; Simvastatin, European Pharmacopoeia (EP) Reference Standard; Simvastatin, United States Pharmacopeia (USP) Reference Standard; Simvastatin, Pharmaceutical Secondary Standard; Certified Reference Material; Simvastatin for peak identification, European Pharmacopoeia (EP) Reference Standard; (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-naphthalenyly-2,2-dimethyl butanoate; (1S,3R,7S,8S,8aR)-8-(2-((2R,4R)-4-Hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbu; (1S,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 2,2-dimethylbutanoate
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Molecular Type
Small molecule
Disease Hypertriglyceridaemia [ICD-11: 5C80] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1.3-2.4 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability
Elimination
13% of the dose was excreted in urine and 60% in feces
Half-life
The concentration or amount of drug in body reduced by one-half in 4.85 hours
Metabolism
The drug is metabolized via a combination of spontaneous chemical conversion and enzyme-mediated hydrolysis by nonspecific carboxyesterases in the intestinal wall, liver, and plasma
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 1.3652 micromolar/kg/day
Water Solubility
The ability of drug to dissolve in water is measured as 0.03 mg/mL
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C25H38O5
PubChem CID
54454
Canonical SMILES
CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C
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
InChIKey
RYMZZMVNJRMUDD-HGQWONQESA-N
CAS Number
CAS 79902-63-9
ChEBI ID
CHEBI:9150
TTD Drug ID
D0H0ND
DrugBank ID
DB00641
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Alpha tricalcium phosphate      Animal bone     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Bilateral 5-mm-diameter calvarial defects were created in adult Wistar rats and filled with preparations of different doses of simvastatin (0, 0.01, 0.1, 0.25 and 0.5 mg) combined with a-TCP particles or left empty.
                    Experimental
                    Result(s)		 When combined with alpha-TCP particles, 0.1 mg simvastatin is the optimal dose for stimulation of the maximum bone regeneration in rat calvarial defects without inducing inflammation.
          Gamma tocotrienol      Bixa orellana     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ERK2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation p38 beta  Molecule Info 
Pathway MAP
                    In-vitro Model Neoplastic mouse +SA mammary epithelial cells Healthy Rattus norvegicus
                    Experimental
                    Result(s)		 Treatment with subeffective doses of simvastatin or gamma-tocotrienol alone had no effect, whereas combined treatment of these compounds resulted in a relatively large decrease in intracellular levels of phosphorylated (activated) MAPK, JNK, p38, and Akt.
          Geraniol      Rosa rugosa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Inhibition Cholesterol biosynthesis
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line.
          Magnesium      Magnesite     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model C57BL/6 male mice were fed with a HFD or a normal-fat diet (NFD).
                    Experimental
                    Result(s)		 The combination of Mg2+ and SIM shows a synergistic effect on attenuating the HFD-induced bone loss.
          Metformin      Galega officinalis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression PRKAA2  Molecule Info 
Pathway MAP
                    In-vitro Model PC-3 D12 CVCL_4Y40 Prostate carcinoma Homo sapiens
LNCaP C4-2B5 CVCL_4788 Prostate carcinoma Homo sapiens
LNCaP C4-2B4 CVCL_4787 Prostate carcinoma Homo sapiens
LNCaP C4-2B3 CVCL_4786 Prostate carcinoma Homo sapiens
MDA-MB-231 CVCL_0062 Breast adenocarcinoma Homo sapiens
                    In-vivo Model Male NCr-nu/nu mice were used in this study.
                    Experimental
                    Result(s)		 Combination of simvastatin and metformin, within pharmacologic dose range (500 nmol/L to 4 umol/L simvastatin and 250 umol/L to 2 mmol/L metformin), significantly and synergistically reduces C4-2B3/B4 CRPC cell viability and metastatic properties, with minimal adverse effects on normal prostate epithelial cells.
          Pinocembrin      Eucalyptus     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vivo Model ApoE / mice (8 weeks old) were fed a high fat diet (21% fat and 0.15% cholesterol).
                    Experimental
                    Result(s)		 The combination of simvastatin and pinocembrin synergistically inhibited atherosclerotic lesion development in ApoE-/- mice with hyperlipidemia, which is partially dependent on the protective of vascular endothelium.
Target and Pathway
Target(s) HMG-CoA reductase (HMGCR)  Molecule Info  [8]
BioCyc Superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate) Click to Show/Hide
2 Superpathway of cholesterol biosynthesis
3 Mevalonate pathway
KEGG Pathway Terpenoid backbone biosynthesis Click to Show/Hide
2 Metabolic pathways
3 Biosynthesis of antibiotics
4 AMPK signaling pathway
5 Bile secretion
NetPath Pathway IL5 Signaling Pathway Click to Show/Hide
2 TGF_beta_Receptor Signaling Pathway
3 TSH Signaling Pathway
Panther Pathway Cholesterol biosynthesis Click to Show/Hide
Pathwhiz Pathway Steroid Biosynthesis Click to Show/Hide
WikiPathways Statin Pathway Click to Show/Hide
2 Regulation of Lipid Metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
3 Activation of Gene Expression by SREBP (SREBF)
4 SREBF and miR33 in cholesterol and lipid homeostasis
5 Integrated Breast Cancer Pathway
6 SREBP signalling
7 Cholesterol Biosynthesis
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2955).
Reference 2 Effects of the combination with alpha-tricalcium phosphate and simvastatin on bone regeneration. Clin Oral Implants Res. 2009 Mar;20(3):280-7.
Reference 3 Synergistic antiproliferative effects of gamma-tocotrienol and statin treatment on mammary tumor cells. Lipids. 2007 Dec;42(12):1113-23.
Reference 4 Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line. Cell Biochem Funct. 2011 Aug;29(6):452-8.
Reference 5 Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss. Bioact Mater. 2021 Feb 3;6(8):2511-2522.
Reference 6 Synergistic simvastatin and metformin combination chemotherapy for osseous metastatic castration-resistant prostate cancer. Mol Cancer Ther. 2014 Oct;13(10):2288-302.
Reference 7 Inhibitory effect of the combination therapy of simvastatin and pinocembrin on atherosclerosis in ApoE-deficient mice. Lipids Health Dis. 2012 Dec 5;11:166.
Reference 8 Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64.
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