Simvastatin
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Basic Info
| Common Name | Simvastatin(F05513) |
| 2D Structure | |
| Description | Simvastatin is a lipid-lowering agent that is derived synthetically from the fermentation of Aspergillus terreus. It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol. |
| FRCD ID | F05513 |
| CAS Number | 79902-63-9 |
| PubChem CID | 54454 |
| Formula | C25H38O5 |
| 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] 2,2-dimethylbutanoate |
| InChI Key | RYMZZMVNJRMUDD-HGQWONQESA-N |
| 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 |
| Canonical SMILES | CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C |
| Isomeric SMILES | CCC(C)(C)C(=O)O[C@H]1C[C@H](C=C2[C@H]1[C@H]([C@H](C=C2)C)CC[C@@H]3C[C@H](CC(=O)O3)O)C |
| Wikipedia | Simvastatin |
| Synonyms |
Lipex
simvastatin
79902-63-9
Zocor
Synvinolin
Sinvacor
Denan
MK-733
Simvastatine
Sivastin
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Lactones |
| Subclass | Delta valerolactones |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Delta valerolactones |
| Alternative Parents | |
| Molecular Framework | Aliphatic heteropolycyclic compounds |
| Substituents | Delta valerolactone - Fatty acid ester - Delta_valerolactone - Dicarboxylic acid or derivatives - Oxane - Fatty acyl - Carboxylic acid ester - Secondary alcohol - Carboxylic acid derivative - Oxacycle - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Alcohol - Organic oxygen compound - Carbonyl group - Aliphatic heteropolycyclic compound |
| 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 418.574 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 7 |
| Complexity | 706 |
| Monoisotopic Mass | 418.272 |
| Exact Mass | 418.272 |
| XLogP | 4.7 |
| Formal Charge | 0 |
| Heavy Atom Count | 30 |
| Defined Atom Stereocenter Count | 7 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9422 |
| Human Intestinal Absorption | HIA+ | 0.9475 |
| Caco-2 Permeability | Caco2- | 0.5951 |
| P-glycoprotein Substrate | Substrate | 0.8508 |
| P-glycoprotein Inhibitor | Inhibitor | 0.7335 |
| Inhibitor | 0.8387 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8435 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7384 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8350 |
| CYP450 2D6 Substrate | Non-substrate | 0.9254 |
| CYP450 3A4 Substrate | Substrate | 0.7513 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9045 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9307 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9025 |
| CYP450 3A4 Inhibitor | Inhibitor | 0.7959 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8682 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.8921 |
| Non-inhibitor | 0.8573 | |
| AMES Toxicity | Non AMES toxic | 0.7920 |
| Carcinogens | Non-carcinogens | 0.9408 |
| Fish Toxicity | High FHMT | 0.9940 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9998 |
| Honey Bee Toxicity | High HBT | 0.8586 |
| Biodegradation | Not ready biodegradable | 0.9657 |
| Acute Oral Toxicity | III | 0.7945 |
| Carcinogenicity (Three-class) | Non-required | 0.7060 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -5.4825 | LogS |
| Caco-2 Permeability | 0.9404 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.0061 | LD50, mol/kg |
| Fish Toxicity | 0.3100 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.3394 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| A transcriptomic analysis of black cohosh: Actein alters cholesterol biosynthesis pathways and synergizes with simvastatin. | Food Chem Toxicol | 2018 Oct | 29969672 |
| A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection. | Toxins (Basel) | 2017 Mar 10 | 28287432 |
| Simultaneous separation of antihyperlipidemic drugs by green ultrahigh-performance liquid chromatography-diode array detector method: Improving the health of liquid chromatography. | J Food Drug Anal | 2017 Apr | 28911687 |
| Statins inhibited the MIP-1α expression via inhibition of Ras/ERK and Ras/Akt pathways in myeloma cells. | Biomed Pharmacother | 2016 Mar | 26898421 |
| Use of Prescription Drug Samples in the USA: A Descriptive Study withConsiderations for Pharmacoepidemiology. | Drug Saf | 2016 Mar | 26798052 |
| High fat diet-induced inflammation and oxidative stress are attenuated byN-acetylneuraminic acid in rats. | J Biomed Sci | 2015 Oct 24 | 26498218 |
| Regulation effect of Aspirin Eugenol Ester on blood lipids in Wistar rats withhyperlipidemia. | BMC Vet Res | 2015 Aug 20 | 26289078 |
| Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo. | J Invest Dermatol | 2015 Apr | 25521459 |
| N-Acetylneuraminic Acid Supplementation Prevents High Fat Diet-Induced InsulinResistance in Rats through Transcriptional and Nontranscriptional Mechanisms. | Biomed Res Int | 2015 | 26688813 |
| Effects of fumonisin B1 alone and combined with deoxynivalenol or zearalenone on porcine granulosa cell proliferation and steroid production. | Theriogenology | 2014 May | 24576714 |
| A method to identify and validate mitochondrial modulators using mammalian cells and the worm C. elegans. | Sci Rep | 2014 Jun 13 | 24923838 |
| Simvastatin modulates cellular components in influenza A virus-infected cells. | Int J Mol Med | 2014 Jul | 24788303 |
| Anti-hypercholesterolemic effect of Pistacia lentiscus fatty oil in egg yolk-fed rabbits: a comparative study with simvastatin. | Chin J Nat Med | 2014 Aug | 25156280 |
| Ezetimibe and simvastatin reduce cholesterol levels in zebrafish larvae fed ahigh-cholesterol diet. | Cholesterol | 2012 | 22693663 |
| The effects of simvastatin or interferon-α on infectivity of human norovirususing a gnotobiotic pig model for the study of antivirals. | PLoS One | 2012 | 22911825 |
| Rapamycin, but not resveratrol or simvastatin, extends life span of geneticallyheterogeneous mice. | J Gerontol A Biol Sci Med Sci | 2011 Feb | 20974732 |
| Lack of robust neurologic benefits with simvastatin or atorvastatin treatmentafter acute thoracic spinal cord contusion injury. | Exp Neurol | 2010 Feb | 19931252 |
| Effects of a trichothecene, T-2 toxin, on proliferation and steroid production by porcine granulosa cells. | Toxicon | 2009 Sep 1 | 19463844 |
| Improvement for high fat diet-induced hepatic injuries and oxidative stress by flavonoid-enriched extract from Nelumbo nucifera leaf. | J Agric Food Chem | 2009 Jul 8 | 19499892 |
| Effects of the flavonol quercetin on the bioavailability of simvastatin in pigs. | Eur J Pharm Sci | 2009 Dec 8 | 19804821 |
Targets
- General Function:
- Protein kinase binding
- Specific Function:
- Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrins alpha-M/beta-2 and alpha-X/beta-2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin alpha-X/beta-2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin alpha-M/beta-2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin alpha-M/beta-2 is also a receptor for factor X. Integrin alpha-D/beta-2 is a receptor for ICAM3 and VCAM1. Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation.
- Gene Name:
- ITGB2
- Uniprot ID:
- P05107
- Molecular Weight:
- 84781.08 Da
References
- Fujii T, Masuyama K, Kawashima K: Simvastatin regulates non-neuronal cholinergic activity in T lymphocytes via CD11a-mediated pathways. J Neuroimmunol. 2006 Oct;179(1-2):101-7. Epub 2006 Jul 10. [16828882 ]
- General Function:
- Oxygen binding
- Specific Function:
- Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
- Gene Name:
- CYP19A1
- Uniprot ID:
- P11511
- Molecular Weight:
- 57882.48 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
- Gene Name:
- AR
- Uniprot ID:
- P10275
- Molecular Weight:
- 98987.9 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
- Gene Name:
- CYP2C19
- Uniprot ID:
- P33261
- Molecular Weight:
- 55930.545 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
- Gene Name:
- NR3C1
- Uniprot ID:
- P04150
- Molecular Weight:
- 85658.57 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- Uniprot ID:
- P05184
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- Gene Name:
- TP53
- Uniprot ID:
- P04637
- Molecular Weight:
- 43652.79 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- 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 ubiquinone and geranylgeranyl proteins.
- Gene Name:
- HMGCR
- Uniprot ID:
- P04035
- Molecular Weight:
- 97475.155 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
- Gene Name:
- NR1I2
- Uniprot ID:
- O75469
- Molecular Weight:
- 49761.245 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]