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

General Information of Drug (ID: DR0991)
Drug Name
TRP-01
Synonyms
Ardeytropin; Indole-3-alanine; L-(-)-Tryptophan; L-Tryptofan; L-tryptophan; L-Tryptophane; L-beta-3-Indolylalanine; L-tryptophan; Lyphan; Optimax; Pacitron; Triptofano [Spanish]; Tryptan; Tryptophan (H-3); Tryptophan (VAN); Tryptophane; Tryptophane [French]; Tryptophanum; Tryptophanum [Latin]; triptofano; trofan; tryptacin; tryptophan; (2S)-2-amino-3-(1H-indol-3-yl)propanoic acid; (S)-Tryptophan; 1-beta-3-Indolylalanine; 1H-Indole-3-alanine; 1beta-3-Indolylalanine; 2-Amino-3-indolylpropanoic acid; 3-Indol-3-ylalanine; 73-22-3; Kalma; L-Trp; h-Trp-oh
Indication Depression [ICD11: 6A71] Phase 1 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 204.22 Topological Polar Surface Area 79.1
Heavy Atom Count 15 Rotatable Bond Count 3
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
6305
PubChem SID
3378 ; 605298 ; 820596 ; 821032 ; 822330 ; 822480 ; 823942 ; 826461 ; 830210 ; 834088 ; 841615 ; 854680 ; 855044 ; 3134836 ; 6435732 ; 6436701 ; 7847088 ; 7888703 ; 7890877 ; 7980851 ; 8026883 ; 8144649 ; 8149576 ; 8153976 ; 10322924 ; 10534147 ; 11109884 ; 11111851 ; 11335632 ; 11360871 ; 11461843 ; 11528964 ; 14710264 ; 14710293 ; 14916602 ; 15195597 ; 17405739 ; 24276916 ; 24277675 ; 24278135 ; 24714971 ; 24770171 ; 24844224 ; 24889916 ; 24900200 ; 24900575 ; 25622645 ; 26703933 ; 26711994 ; 26712808
ChEBI ID
ChEBI:16828
CAS Number
73-22-3
TTD Drug ID
D05EJG
Formula
C11H12N2O2
Canonical SMILES
C1=CC=C2C(=C1)C(=CN2)CC(C(=O)O)N
InChI
1S/C11H12N2O2/c12-9(11(14)15)5-7-6-13-10-4-2-1-3-8(7)10/h1-4,6,9,13H,5,12H2,(H,14,15)/t9-/m0/s1
InChIKey
QIVBCDIJIAJPQS-VIFPVBQESA-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
Indole-pyruvate DM003570
129900254
Unclear 1 [2]
Melatonin DM003572
896
Unclear 1 [2]
N-formyl-kynurenine DM003558
910
Unclear 1 [2]
Indole-pyruvate derivatives DM003571 N. A. Unclear 2 [2]
L-kynurenine DM003559
161166
Unclear 2 [2]
Melatonin Derivatives DM003573 N. A. Unclear 2 [2]
3-hydroxy-kynurenine DM003567
11811
Unclear 3 [2]
Anthranilate DM003560
227
Unclear 3 [2]
Kynurenate DM003569
3845
Unclear 3 [2]
3-hydroxy-Anthranilate DM003561
86
Unclear 4 [2]
3-hydroxy-Anthranilate DM003561
86
Unclear 4 [14]
5-hydroxy-anthranilic acid DM003566
129847949
Unclear 4 [14]
Xanthurenic acid DM003568
5699
Unclear 4 [14]
2-amino-3-muconicsemi-aldehyde DM003562 N. A. Unclear 5 [2]
2-amino-3-muconicsemi-aldehyde DM003562 N. A. Unclear 5 [14]
Acetyl Coenzyme A DM003095
444493
Unclear 6 [2]
Acetyl Coenzyme A DM003095
444493
Unclear 6 [14]
Picolinate DM003565
6920223
Unclear 6 [2]
Picolinate DM003565
6920223
Unclear 6 [14]
Quinolate DM003563
54598431
Unclear 6 [2]
Quinolate DM003563
54598431
Unclear 6 [14]
NAD+ de novo biosynthesis DM003564 N. A. Unclear 7 [2]
NAD+ de novo biosynthesis DM003564 N. A. Unclear 7 [14]
⏷ Show the Full List of 23  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR003996 TRP-01 N-formyl-kynurenine Unclear IDO1 ... [2]
MR004010 TRP-01 Indole-pyruvate Unclear IL4i1 [2]
MR004012 TRP-01 Melatonin Unclear TPH1 [2]
MR004011 Indole-pyruvate Indole-pyruvate derivatives Unclear Unclear [2]
MR004013 Melatonin Melatonin Derivatives Unclear Unclear [2]
MR003997 N-formyl-kynurenine L-kynurenine Unclear AFMID [2]
MR003998 L-kynurenine Anthranilate Unclear KYNU [2]
MR004006 L-kynurenine 3-hydroxy-kynurenine Unclear KMO [2]
MR004009 L-kynurenine Kynurenate Unclear KATs [2]
MR004007 3-hydroxy-kynurenine 3-hydroxy-Anthranilate Unclear KYNU [2]
MR004008 3-hydroxy-kynurenine Xanthurenic acid Unclear Unclear [14]
MR003999 Anthranilate 3-hydroxy-Anthranilate Unclear Unclear [14]
MR004005 Anthranilate 5-hydroxy-anthranilic acid Unclear Unclear [14]
MR004000 3-hydroxy-Anthranilate 2-amino-3-muconicsemi-aldehyde Unclear Unclear [14]
MR004001 2-amino-3-muconicsemi-aldehyde Quinolate Unclear Unclear [14]
MR004003 2-amino-3-muconicsemi-aldehyde Acetyl-CoA Unclear Unclear [14]
MR004004 2-amino-3-muconicsemi-aldehyde Picolinate Unclear Unclear [14]
MR004002 Quinolate NAD+ de novo biosynthesis Unclear Unclear [14]
⏷ Show the Full List of 18 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
3-hydroxyanthranilate 3,4-dioxygenase (HAAO) DMEN133 Homo sapiens
3HAO_HUMAN
1.13.11.6
[2]
DOPA decarboxylase (DDC) DME0125 Homo sapiens
DDC_HUMAN
4.1.1.28
[3]
Indoleamine 2,3-dioxygenase 1 (IDO1) DME0171 Homo sapiens
I23O1_HUMAN
1.13.11.52
[4]
Indoleamine 2,3-dioxygenase 2 (IDO2) DME0459 Homo sapiens
I23O2_HUMAN
1.13.11.52
[4]
Kynureninase (KYNU) DMEN131 Homo sapiens
KYNU_HUMAN
3.7.1.3
[2]
Kynurenine 3-monooxygenase (KMO) DMEN132 Homo sapiens
KMO_HUMAN
1.14.13.9
[2]
kynurenine aminotransferases (KATs) DMEN134 Homo sapiens Not Available Not Available [2]
Kynurenine formamidase (AFMID) DMEN130 Homo sapiens
KFA_HUMAN
3.5.1.9
[2]
L-amino-acid oxidase (IL4I1) DMEN135 Homo sapiens
OXLA_HUMAN
1.4.3.2
[2]
Tryptophan 5-hydroxylase 1 (TPH1) DME0173 Homo sapiens
TPH1_HUMAN
1.14.16.4
[5]
Tryptophan 5-hydroxylase 2 (TPH2) DME0174 Homo sapiens
TPH2_HUMAN
1.14.16.4
[6]
Tryptophan oxygenase (TRPO) DME0172 Homo sapiens
T23O_HUMAN
1.13.11.11
[7]
Tryptophan oxygenase (TRPO) DME0172 Homo sapiens
T23O_HUMAN
1.13.11.11
[2]
Tryptophanyl-tRNA synthetase cytoplasmic (WARS1) DME0175 Homo sapiens
SYWC_HUMAN
6.1.1.2
[8]
Tryptophanyl-tRNA synthetase mitochondrial (WARS2) DME0176 Homo sapiens
SYWM_HUMAN
6.1.1.2
[9]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1254 Bacteroides thetaiotaomicron Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1259 Intestinibacter bartlettii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1267 Anaerobutyricum hallii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1366 Bacteroides eggerthii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1376 Bacteroides ovatus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1445 Parabacteroides distasonis Not Available Not Available [10]
⏷ Show the Full List of 22  DME(s)
Experimental Enzyme Kinetic Data of This Drug
DME Name DME Info Kinetic Data Uniprot ID REF
Indoleamine 2,3-dioxygenase 1 (IDO1) DME0171 Km = 0.0141 microM
I23O1_HUMAN
[11]
Indoleamine 2,3-dioxygenase 2 (IDO2) DME0459 Km = 0.02 microM
I23O2_HUMAN
[4]
Tryptophan 5-hydroxylase 2 (TPH2) DME0174 Km = 0.0186 microM
TPH2_HUMAN
[12]
Tryptophanyl-tRNA synthetase mitochondrial (WARS2) DME0176 Km = 0.027 microM
SYWM_HUMAN
[13]
References
1 Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198.
2 Tryptophan and indole metabolism in immune regulation
3 Origin and metabolism of serotonin. J Cardiovasc Pharmacol. 1990;16 Suppl 3:S1-7.
4 Kynurenine pathway metabolites and enzymes involved in redox reactions. Neuropharmacology. 2017 Jan;112(Pt B):331-345.
5 Developmental role of tryptophan hydroxylase in the nervous system. Mol Neurobiol. 2007 Feb;35(1):45-54.
6 Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity. J Neurochem. 2007 Nov;103(3):1111-20.
7 Reaction pathway of tryptophanase-catalyzed L-tryptophan synthesis from D-serine. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Nov 1;879(29):3289-95.
8 IFN-gamma-induced IDO and WRS expression in microglia is differentially regulated by IL-4. Glia. 2007 Oct;55(13):1385-96.
9 Crystal structure of tryptophanyl-tRNA synthetase complexed with adenosine-5' tetraphosphate: evidence for distributed use of catalytic binding energy in amino acid activation by class I aminoacyl-tRNA synthetases. J Mol Biol. 2007 May 25;369(1):108-28.
10 Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol Nutr Food Res. 2013 Mar;57(3):523-35.
11 Purification and kinetic characterization of human indoleamine 2,3-dioxygenases 1 and 2 (IDO1 and IDO2) and discovery of selective IDO1 inhibitors. Biochim Biophys Acta. 2011 Dec;1814(12):1947-54.
12 Characterization of wild-type and mutant forms of human tryptophan hydroxylase 2. J Neurochem. 2007 Mar;100(6):1648-57.
13 Identification and characterization of human mitochondrial tryptophanyl-tRNA synthetase. J Biol Chem. 2000 Jun 2;275(22):16820-6.
14 Neurotoxicity of tryptophan metabolites

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