Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR1485)
Drug Name
Simvastatin
Prodrug Info Simvastatin is the prodrug of Simvastatin hydroxy acid
Synonyms
Simcard; Simlup; Simovil; Simvacor; Simvastatin (Zocor); Simvastatin lactone; Simvastatina; Simvastatina [Spanish]; Simvastatine; Simvastatine [French]; Simvastatinum; Simvastatinum [Latin]; Simvoget; Sinvacor; Sivastin; Synvinolin; Cholestat; Coledis; Colemin; Corolin; Labistatin; Lipovas; Lodales; MK-0733; MK-733; Medipo; Nivelipol; Pantok; Rechol; Rendapid; Vasotenal; Velostatin; Zocord; Zorced; simvastatin; 79902-63-9; Denan; Lipex; Zocor
Indication Dyslipidaemia [ICD11: 5C81] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 418.6 Topological Polar Surface Area 72.8
Heavy Atom Count 30 Rotatable Bond Count 7
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 5
Cross-matching ID
PubChem CID
54454
PubChem SID
496592 ; 648581 ; 7847500 ; 7980599 ; 8183649 ; 10321271 ; 10852028 ; 11113242 ; 11342166 ; 11362349 ; 11364611 ; 11367173 ; 11369735 ; 11371657 ; 11374383 ; 11377897 ; 11466893 ; 11468013 ; 11485617 ; 11486566 ; 11487751 ; 11489487 ; 11490485 ; 11492447 ; 11495531 ; 11528633 ; 11533326 ; 12013879 ; 12146013 ; 14831549 ; 14929313 ; 24724617 ; 25819951 ; 26612685 ; 26680673 ; 26759532 ; 34718442 ; 46508654 ; 47365442 ; 47440515 ; 47736737 ; 47885633 ; 47885634 ; 48110715 ; 48334759 ; 48416540 ; 49698671 ; 50086525 ; 50100555 ; 50100556
ChEBI ID
ChEBI:9150
CAS Number
79902-63-9
TTD Drug ID
D0H0ND
Formula
C25H38O5
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
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
6'-beta-Hydroxysimvastatin DM006339
102329664
Oxidation - Aliphatic hydroxylation 1 [8]
6-Exomethylenesimvastatin DM006341
15925972
Oxidation - Dehydrogenation 1 [9]
Pravastatin 3,5-dihydrodiol DM006340
101598494
Oxidation - Aliphatic hydroxylation 1 [8]
Simvastatin hydroxy acid DM006338
64718
Oxidation - 3'-hydroxylation 1 [5]
Unclear DM009999 N. A. Unclear 1 [9]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR013433 Simvastatin Simvastatin hydroxy acid Oxidation - 3'-hydroxylation CYP3A4 ... [5]
MR013434 Simvastatin 6'-beta-Hydroxysimvastatin Oxidation - Aliphatic hydroxylation CYP2C8 ... [8]
MR013435 Simvastatin Pravastatin 3,5-dihydrodiol Oxidation - Aliphatic hydroxylation CYP3A4 ... [8]
MR013436 Simvastatin 6-Exomethylenesimvastatin Oxidation - Dehydrogenation CYP3A4 ... [9]
MR013437 Simvastatin Unclear Unclear UGT1A1 ... [9]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[3]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[3]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[7]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[7]
⏷ Show the Full List of 12  DME(s)
References
1 Simvastatin was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006 Dec;80(6):565-81.
3 DrugBank(Pharmacology-Metabolism):Simvastatin
4 Genetic polymorphisms in cytochrome P450 enzymes: effect on efficacy and tolerability of HMG-CoA reductase inhibitors. Am J Cardiovasc Drugs. 2004;4(4):247-55.
5 A comparison of the effects of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors on the CYP3A4-dependent oxidation of mexazolam in vitro. Drug Metab Dispos. 2001 Mar;29(3):282-8.
6 In vitro metabolism of simvastatin in humans [SBT]identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos. 1997 Oct;25(10):1191-9.
7 Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.
8 Cytochromes P450: a structure-based summary of biotransformations using representative substrates Drug Metab Rev. 2008;40(1):1-100. doi: 10.1080/03602530802309742.
9 Simvastatin Tablet, Film-Coated

If you find any error in data or bug in web service, please kindly report it to Dr. Yin and Dr. Li.