Details of the Drug

General Information of Drug (ID: DMW3QGJ)

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
Disease Entry ICD 11 Status REF
Primary sclerosing cholangitis DB96.2 Phase 1/2 [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 176.17
Topological Polar Surface Area (xlogp) 1.9
Rotatable Bond Count (rotbonds) 0
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
Chemical Identifiers
Formula
C10H8O3
IUPAC Name
7-hydroxy-4-methylchromen-2-one
Canonical SMILES
CC1=CC(=O)OC2=C1C=CC(=C2)O
InChI
HSHNITRMYYLLCV-UHFFFAOYSA-N
InChIKey
1S/C10H8O3/c1-6-4-10(12)13-9-5-7(11)2-3-8(6)9/h2-5,11H,1H3
Cross-matching ID
PubChem CID
5280567
ChEBI ID
CHEBI:17224
CAS Number
90-33-5
DrugBank ID
DB07118
INTEDE ID
DR0841

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [2]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Substrate [3]
UDP-glucuronosyltransferase 1A6 (UGT1A6) DESD26P UD16_HUMAN Substrate [4]
UDP-glucuronosyltransferase 1A4 (UGT1A4) DELOY3P UD14_HUMAN Substrate [4]
UDP-glucuronosyltransferase 2B11 (UGT2B11) DE7TIN4 UDB11_HUMAN Substrate [5]
UDP-glucuronosyltransferase 1A5 (UGT1A5) DEPF954 UD15_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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 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.
4 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.
5 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.
6 A common polymorphic variant of UGT1A5 displays increased activity due to optimized cofactor binding. FEBS Lett. 2018 Jun;592(11):1837-1846.
7 Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
8 Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
9 Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
10 UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
11 Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
12 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
13 Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
14 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
15 Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
16 Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
17 Polymorphic expression of UGT1A9 is associated with variable acetaminophen glucuronidation in neonates: a population pharmacokinetic and pharmacogenetic study. Clin Pharmacokinet. 2018 Oct;57(10):1325-1336.
18 Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
19 Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.
20 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.
21 The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24.
22 The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83.
23 FDA label of Lorlatinib. The 2020 official website of the U.S. Food and Drug Administration.
24 Studies on induction of lamotrigine metabolism in transgenic UGT1 mice. Xenobiotica. 2009 Nov;39(11):826-35.
25 Human biotransformation of the nonnucleoside reverse transcriptase inhibitor rilpivirine and a cross-species metabolism comparison. Antimicrob Agents Chemother. 2013 Oct;57(10):5067-79.
26 Identification of human UDP-glucuronosyltransferases catalyzing hepatic 1alpha,25-dihydroxyvitamin D3 conjugation. Biochem Pharmacol. 2008 Mar 1;75(5):1240-50.
27 Bevirimat: a novel maturation inhibitor for the treatment of HIV-1 infection. Antivir Chem Chemother. 2008;19(3):107-13.
28 UGT1A6 and UGT2B15 polymorphisms and acetaminophen conjugation in response to a randomized, controlled diet of select fruits and vegetables. Drug Metab Dispos. 2011 Sep;39(9):1650-7.
29 UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther. 2005 Jun;313(3):1340-6.
30 Pharmacokinetics of propofol and extrahepatic UGT1A6 gene expression in anhepatic rats. Pharmacology. 2009;84(4):219-26.
31 Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
32 Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria. Allergy Asthma Immunol Res. 2011 Oct;3(4):273-6.
33 S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen. Br J Clin Pharmacol. 2005 Oct;60(4):423-33.
34 Deferiprone glucuronidation by human tissues and recombinant UDP glucuronosyltransferase 1A6: an in vitro investigation of genetic and splice variants. Drug Metab Dispos. 2009 Feb;37(2):322-9.
35 Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab Rev. 1999 Nov;31(4):817-99.
36 Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells. Pharmacogenetics. 2004 Aug;14(8):487-99.