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

General Information of Drug (ID: DR0841)
Drug Name
LM-94
Synonyms
Bilcolic; Bilicante; Hymecromone; Cantabilin; Cantabiline; Cholestil; Cholonerton; Coumarin 4; Crodimon; Cumarote-C; Eurogale; Himecromona; Hymecromon; Hymecromonum; Imecromone; Imecromone [DCIT]; Medilla; Mendiaxon; Omega 127; Pilot 447; Resocyanine; beta-Methylumbelliferone; 2H-1-Benzopyran-2-one, 7-hydroxy-4-methyl-; 4-MU; 4-Methyl-7-hydroxycoumarin; 4-Methylumbelliferon; 4-methylumbelliferone; 7-HYDROXY-4-METHYLCOUMARIN; 7-Hydroxy-4-methyl-2-oxo-2H-1-benzopyran; 7-Hydroxy-4-methyl-2H-chromen-2-one; 90-33-5; LM 94; NSC 19026; NSC 9408
Indication Cholangitis [ICD11: DC13] Phase 1/2 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 176.17 Topological Polar Surface Area 46.5
Heavy Atom Count 13 Rotatable Bond Count 0
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 3
Cross-matching ID
PubChem CID
5280567
ChEBI ID
CHEBI:17224
CAS Number
90-33-5
Formula
C10H8O3
Canonical SMILES
CC1=CC(=O)OC2=C1C=CC(=C2)O
InChI
1S/C10H8O3/c1-6-4-10(12)13-9-5-7(11)2-3-8(6)9/h2-5,11H,1H3
InChIKey
HSHNITRMYYLLCV-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
4-Methylumbelliferone sulfate DM005749
84843
Conjugation - Conjugation 1 [7]
4-Methylumbelliferyl glucuronide DM005750
91553
Conjugation - Conjugation 1 [8]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR006134 LM-94 4-Methylumbelliferone sulfate Conjugation - Conjugation SULT [7]
MR006135 LM-94 4-Methylumbelliferyl glucuronide Conjugation - Conjugation UGT1A1 ... [8]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Homo sapiens
UD14_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 1A5 (UGT1A5) DME0602 Homo sapiens
UD15_HUMAN
2.4.1.17
[4]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DME0072 Homo sapiens
UD16_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[5]
UDP-glucuronosyltransferase 2B11 (UGT2B11) DME0640 Homo sapiens
UDB11_HUMAN
2.4.1.17
[6]
⏷ Show the Full List of 6  DME(s)
Experimental Enzyme Kinetic Data of This Drug
DME Name DME Info Kinetic Data Uniprot ID REF
UDP-glucuronosyltransferase 1A4 (UGT1A4) DME0048 Km = 0.00012 microM
UD14_HUMAN
[3]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DME0072 Km = 0.00012 microM
UD16_HUMAN
[3]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Km = 0.0029 microM
UD19_HUMAN
[5]
References
1 ClinicalTrials.gov (NCT02780752) A Study of Oral Hymecromone to Treat Adults With Primary Sclerosing Cholangitis.
2 In vitro inhibitory effects of non-steroidal anti-inflammatory drugs on 4-methylumbelliferone glucuronidation in recombinant human UDP-glucuronosyltransferase 1A9--potent inhibition by niflumic acid. Biopharm Drug Dispos. 2006 Jan;27(1):1-6.
3 Identification of aspartic acid and histidine residues mediating the reaction mechanism and the substrate specificity of the human UDP-glucuronosyltransferases 1A. J Biol Chem. 2007 Dec 14;282(50):36514-24.
4 A common polymorphic variant of UGT1A5 displays increased activity due to optimized cofactor binding. FEBS Lett. 2018 Jun;592(11):1837-1846.
5 The "albumin effect" and drug glucuronidation: bovine serum albumin and fatty acid-free human serum albumin enhance the glucuronidation of UDP-glucuronosyltransferase (UGT) 1A9 substrates but not UGT1A1 and UGT1A6 activities. Drug Metab Dispos. 2008 Jun;36(6):1056-62.
6 cDNA cloning and expression of two new members of the human liver UDP-glucuronosyltransferase 2B subfamily. Biochem Biophys Res Commun. 1993 Jul 15;194(1):496-503.
7 [Metabolism of lomerizine hydrochloride (KB-2796) in rats]
8 Comparisons of detections, stabilities, and kinetics of degradation of hymecromone and its glucuronide and sulfate metabolites

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