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

General Information of Drug (ID: DR1132)
Drug Name
Nateglinide
Synonyms
Nateglinide [INN]; SDZ DJN 608; SDZ-DJN 608; SDZ-DJN-608; Starlix; Starsis; Trazec; Nateglinide; DJN 608; DJN-608; Fastic; Senaglinide; (-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine; (2R)-3-phenyl-2-[(4-propan-2-ylcyclohexanecarbonyl)amino]propanoic acid; 105816-04-4; 105816-06-6; 41X3PWK4O2; A 4166; A-4166; AY 4166; AY-4166; AY4166; CHEBI:31897; CHEMBL783; MFCD00875706; N-[(trans-4-Isopropylcyclohexyl)carbonyl]-D-phenylalanine; N-{[trans-4-(propan-2-yl)cyclohexyl]carbonyl}-D-phenylalanine; UNII-41X3PWK4O2
Indication Diabetes mellitus [ICD11: 5A10] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 317.4 Topological Polar Surface Area 66.4
Heavy Atom Count 23 Rotatable Bond Count 6
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
5311309
PubChem SID
582898 ; 7848174 ; 7980094 ; 12013966 ; 14752539 ; 14874578 ; 26719880 ; 37101837 ; 39341005 ; 46386701 ; 46504836 ; 49681657 ; 49830241 ; 56313768 ; 57359430 ; 75919327 ; 81092826 ; 91748929 ; 92308370 ; 92308686 ; 92711649 ; 93166415 ; 103206766 ; 104253649 ; 114155796 ; 117890894 ; 124658899 ; 124757828 ; 124801358 ; 125164632 ; 126630653 ; 126657177 ; 128797137 ; 128797139 ; 128797141 ; 131293719 ; 131347903 ; 131860350 ; 135692483 ; 136949105 ; 137129256 ; 137175459 ; 137231395 ; 140330680 ; 142491149 ; 142619974 ; 143248460 ; 144204985 ; 151981031 ; 152100318
ChEBI ID
CHEBI:31897
CAS Number
105816-04-4
TTD Drug ID
D06PSS
Formula
C19H27NO3
Canonical SMILES
CC(C)C1CCC(CC1)C(=O)NC(CC2=CC=CC=C2)C(=O)O
InChI
1S/C19H27NO3/c1-13(2)15-8-10-16(11-9-15)18(21)20-17(19(22)23)12-14-6-4-3-5-7-14/h3-7,13,15-17H,8-12H2,1-2H3,(H,20,21)(H,22,23)/t15-,16-,17-/m1/s1
InChIKey
OELFLUMRDSZNSF-OFLPRAFFSA-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
2-{[4-(1-hydroxypropan-2-yl)cyclohexyl]formamido}-3-phenylpropanoic acid DM004552 N. A. Oxidation - Aliphatic hydroxylation 1 [5]
2-{[4-(2-hydroxypropan-2-yl)cyclohexyl]formamido}-3-phenylpropanoic acid DM004553 N. A. Oxidation - Aliphatic hydroxylation 1 [5]
Nateglinide glucuronide and isomers (M4/M5/M6) DM004551 N. A. Conjugation - Glucuronidation 1 [5]
Nateglinide metabolite M1 DM004549
91511538
Oxidation - Hydrolyzationn 1 [5]
Nateglinide metabolite M2/M3 DM004547
91667679
Oxidation - Hydrolyzationn 1 [5] , [7]
Nateglinide metabolite M7 DM004550
91667711
Oxidation - Oxidationn 1 [5]
Nateglinide metabolite M11/M12 DM004548
91667686
Oxidation - Hydrolyzationn 2 [5]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR004876 Nateglinide Nateglinide metabolite M2/M3 Oxidation - Hydrolyzationn CYP2C9 ... [5], [7]
MR004878 Nateglinide Nateglinide metabolite M1 Oxidation - Hydrolyzationn CYP2C9 ... [5]
MR004880 Nateglinide Nateglinide metabolite M7 Oxidation - Oxidationn Unclear [5]
MR004882 Nateglinide Nateglinide glucuronide and isomers (M4/M5/M6) Conjugation - Glucuronidation UGT2A1 [5]
MR004883 Nateglinide 2-{[4-(1-hydroxypropan-2-yl)cyclohexyl]formamido}-3-phenylpropanoic acid Oxidation - Aliphatic hydroxylation CYP2C9 ... [5]
MR004884 Nateglinide 2-{[4-(2-hydroxypropan-2-yl)cyclohexyl]formamido}-3-phenylpropanoic acid Oxidation - Aliphatic hydroxylation CYP2C9 ... [5]
MR004879 Nateglinide metabolite M1 Nateglinide metabolite M11/M12 Oxidation - Hydrolyzationn Unclear [5]
MR004877 Nateglinide metabolite M2/M3 Nateglinide metabolite M11/M12 Oxidation - Hydrolyzationn Unclear [5]
MR004881 Nateglinide metabolite M7 Nateglinide metabolite M11/M12 Oxidation - Hydrolyzationn Unclear [5]
⏷ Show the Full List of 9 MR(s)
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
[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
[4]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[5]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[5]
UDP-glucuronosyltransferase 2A1 (UGT2A1) DME0622 Homo sapiens
UD2A1_HUMAN
2.4.1.17
[5]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1254 Bacteroides thetaiotaomicron Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1366 Bacteroides eggerthii Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1402 Clostridium botulinum Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1444 Odoribacter splanchnicus Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1445 Parabacteroides distasonis Not Available Not Available [6]
Unclear metabolic mechanism (DME-unclear) DME1447 Parabacteroides merdae Not Available Not Available [6]
⏷ Show the Full List of 19  DME(s)
References
1 Nateglinide was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Drug-drug and food-drug pharmacokinetic interactions with new insulinotropic agents repaglinide and nateglinide. Clin Pharmacokinet. 2007;46(2):93-108.
3 Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers. Clin Pharmacokinet. 2004;43(4):267-78.
4 Drug Interactions Flockhart Table
5 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.
6 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
7 Pharmacokinetics of nateglinide enantiomers and their metabolites in Goto-Kakizaki rats, a model for type 2 diabetes mellitus

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