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

General Information of Drug (ID: DR1481)
Drug Name
Sildenafil citrate
Synonyms
Sildenafil (citrate); Sildenafil citrate; Sildenafil citrate [USAN]; Sildenafil citrate salt; UK 92480; UK-92480-10; UNII-BW9B0ZE037; Sildenafilcitrate; Sildenafil; 1-((3-(4,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine; 139755-83-2; 3M7OB98Y7H; 5-(2-Ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one; BNRNXUUZRGQAQC-UHFFFAOYSA-N; C22H30N6O4S; CHEBI:9139; CHEMBL192; HSDB 7305; Sildenafil [INN:BAN]; UK-92,480-10; UK-92480; UNII-3M7OB98Y7H; 1-((3-(6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-5-yl)-4-ethoxyphenyl)sulfonyl)-4-methylpiperazine citrate (1:1); 171599-83-0; BW9B0ZE037; CHEBI:58987; Caverta; DSSTox_CID_26076; DSSTox_GSID_46076; DSSTox_RID_81321
Indication Erectile dysfunction [ICD11: HA01] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 666.7 Topological Polar Surface Area 250
Heavy Atom Count 46 Rotatable Bond Count 12
Hydrogen Bond Donor Count 5 Hydrogen Bond Acceptor Count 15
Cross-matching ID
PubChem CID
135413523
ChEBI ID
CHEBI:31307
CAS Number
171599-83-0
Formula
C28H38N6O11S
Canonical SMILES
CCCC1=NN(C2=C1N=C(NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)C)OCC)C.C(C(=O)O)C(CC(=O)O)(C(=O)O)O
InChI
1S/C22H30N6O4S.C6H8O7/c1-5-7-17-19-20(27(4)25-17)22(29)24-21(23-19)16-14-15(8-9-18(16)32-6-2)33(30,31)28-12-10-26(3)11-13-28;7-3(8)1-6(13,5(11)12)2-4(9)10/h8-9,14H,5-7,10-13H2,1-4H3,(H,23,24,29);13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
InChIKey
DEIYFTQMQPDXOT-UHFFFAOYSA-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
N-dealkyl Sildenafil DM001316
136622597
Oxidation - N-Dealkylation 1 [2]
N-desmethyl Sildenafil DM001315
135455980
Oxidation - N-Demethylation 1 [4] , [8] , [3]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002252 Sildenafil citrate Desmethylsildenafil Oxidation - N-Demethylation CYP3A4 ... [4], [8], [3]
MR002253 Sildenafil citrate N-dealkyl Sildenafil Oxidation - N-Dealkylation CYP3A4 ... [2]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[2]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[2]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[5]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[6]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1398 Clostridioides difficile Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1402 Clostridium botulinum Not Available Not Available [7]
⏷ Show the Full List of 10  DME(s)
References
1 Sildenafil Citrate was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
3 Erectile dysfunction drugs changed the protein expressions and activities of drug-metabolising enzymes in the liver of male rats. Oxid Med Cell Longev. 2016;2016:4970906.
4 The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008 Jun;36(6):986-90.
5 Drug Interactions Flockhart Table
6 Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol. 2001 Mar;51(3):239-48.
7 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
8 Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol. 2002;53 Suppl 1(Suppl 1):5S-12S. doi: 10.1046/j.0306-5251.2001.00027.x.

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