HYMECROMONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H8O3
Molecular Weight	176.1687
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC(=O)OC2=C1C=CC(O)=C2

InChI

InChIKey=HSHNITRMYYLLCV-UHFFFAOYSA-N

InChI=1S/C10H8O3/c1-6-4-10(12)13-9-5-7(11)2-3-8(6)9/h2-5,11H,1H3

HIDE SMILES / InChI

Description
Sources: https://www.sopharma.com/hymecromon.php
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/25852691

Hymecromone (4-methylumbelliferone) is already approved drug in Europe and Asia where it is used to treat biliary spasm. It is used as choleretic and antispasmodic drugs and as a standard for the fluorometric determination of enzyme activity. The concomitant administration of Hymecromone with products, containing metoclopramide, leads to mutual decrease of their action. Due to a danger of diarrhea with subsequent hypokalemia, Hymecromone should be applied with caution to patients on cardiac glycosides therapy (in these cases the sensitivity to them is increased). Hymecromone can be administered simultaneously with otherspasmolytics and analgesics. Very rare allergic reactions, itching, erythema, rashes; diarrhea which normally disappears by reduction of dose or discontinuance of therapy.

Approval Year

Conditions

Condition	Modality	Targets	Highest Phase	Product
Biliary duct dyskinesia 3 Sources: https://www.sopharma.com/hymecromon.php	Primary		Approved 8583	Unknown Approved Use Unknown
Chronic cholecystitis 3 Sources: https://www.sopharma.com/hymecromon.php	Primary		Approved 8583	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
306 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8427942/	400 mg single, intravenous dose: 400 mg route of administration: Intravenous experiment type: SINGLE co-administered:		HYMECROMONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
385 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8427942/	800 mg single, intravenous dose: 800 mg route of administration: Intravenous experiment type: SINGLE co-administered:		HYMECROMONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1067.58 mg single, oral Highest studied dose Dose: 1067.58 mg Route: oral Route: single Dose: 1067.58 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8427942/	healthy Health Status: healthy Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/8427942/	Sources: https://pubmed.ncbi.nlm.nih.gov/8427942/
711.72 mg single, intravenous Highest studied dose Dose: 711.72 mg Route: intravenous Route: single Dose: 711.72 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8427942/	healthy Health Status: healthy Sex: M Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/8427942/	Sources: https://pubmed.ncbi.nlm.nih.gov/8427942/
400 mg single, oral Recommended Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/	unknown Health Status: unknown Sex: F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/	Disc. AE: Pruritus cutaneous, Angioedema... Other AEs: Urticaria... AEs leading to discontinuation/dose reduction: Pruritus cutaneous (1 pt) Angioedema (1 pt) Other AEs: Urticaria (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/

AEs

AE	Significance	Dose	Population
Urticaria	1 pt	400 mg single, oral Recommended Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/	unknown Health Status: unknown Sex: F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/
Angioedema	1 pt Disc. AE	400 mg single, oral Recommended Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/	unknown Health Status: unknown Sex: F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/
Pruritus cutaneous	1 pt Disc. AE	400 mg single, oral Recommended Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/	unknown Health Status: unknown Sex: F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/8837673/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP2C19 2057 CYP1A2 2153 CYP19A1 429 UMAT 30	MRP3 58 UGT1A1 479 UGT1A10 331 UGT1A7 249 UGT1A3 470 BCRP 697 MRP2 252 rSULTs 3 UGT2B15 236 UGT2B7 456 UGT1A8 323 UGT1A4 399 MRP4 91 UGT1A9 423 UGT1A6 343 UGT2B17 237

Drug as perpetrator

Target	Modality	Activity
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144203936	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/899#sid=11112236	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/883#sid=11112236	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/891#sid=11112236	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144203936	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/884#sid=11112236	no
UMAT 30	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/602162#sid=47193740	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671199#sid=170465819	yes [IC50 17.3768 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/26934120/	yes

Drug as victim

Target	Modality	Activity	Metabolite
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	no
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28850245/	unlikely	4-MUG 3
MRP2 252	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28850245/	unlikely	4-MUG 3
rSULTs 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/2005878/	yes [Km 1.1 uM]
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 109 uM]
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 113 uM]
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 1159 uM]
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 14 uM]
MRP4 91	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28850245/	yes [Km 168 uM]	4-MUG 3
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 253 uM]
MRP3 58	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28850245/	yes [Km 278 uM]	4-MUG 3
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 31 uM]
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26708612/ \| https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 335 uM]
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 4204 uM]
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 730 uM]
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15039294/	yes [Km 8 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=144203936

PubMed

Title	Date	PubMed
A novel efflux-recapture process underlies the mechanism of high-density lipoprotein cholesteryl ester-selective uptake mediated by the low-density lipoprotein receptor-related protein.	2004-09	15178567
Risk factors for periodontitis in HIV patients.	2004-06	15102043
Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases.	2004-05-27	15161036
Aldehyde detection by chromogenic/fluorogenic oxime bond fragmentation.	2004-05-21	15136802
Molecular characterization of membrane type and ganglioside-specific sialidase (Neu3) expressed in E. coli.	2004-04-30	15179041
Development of novel conductometric biosensors based on immobilised whole cell Chlorella vulgaris microalgae.	2004-04-15	15018964
Pharmacological enhancement of beta-hexosaminidase activity in fibroblasts from adult Tay-Sachs and Sandhoff Patients.	2004-04-02	14724290
DNA damage in healthy term neonate.	2004-04	15113635
Human udp-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid.	2004-04	15039294
Susceptibility of human influenza viruses from Australasia and South East Asia to the neuraminidase inhibitors zanamivir and oseltamivir.	2004-04	15026200
Expression of chitinase-encoding genes in Bacillus thuringiensis and toxicity of engineered B. thuringiensis subsp. aizawai toward Lymantria dispar larvae.	2004-03	15057461
Stability of the complexes of some lanthanides with coumarin derivatives. I. Cerium(III)-4-methyl-7-hydroxycoumarin.	2004-03	15050043
Synthesis and biological activity of substituted 2,4,6-s-triazines.	2004-03	15050040
Structure of the haemagglutinin-neuraminidase from human parainfluenza virus type III.	2004-01-30	14729348
Evidence that unsaturated fatty acids are potent inhibitors of renal UDP-glucuronosyltransferases (UGT): kinetic studies using human kidney cortical microsomes and recombinant UGT1A9 and UGT2B7.	2004-01-01	14667942
Identification of aryl-phospho-beta-D-glucosidases in Bacillus subtilis.	2004-01	14652714
Mechanism of the hydrolysis of 4-methylumbelliferyl-beta-D-glucoside by germinating and outgrowing spores of Bacillus species.	2004	15139916
[A case of successful use of odeston in the diagnostics and treatment of biliary dysfunctional disorders].	2003-12	14982008
Inhibition of rat liver sulfotransferases SULT1A1 and SULT2A1 and glucuronosyltransferase by dietary flavonoids.	2003-12	14742143
Potent bivalent inhibition of human tryptase-beta by a synthetic inhibitor.	2003-12	14719803
Verapamil regulates activity and mRNA-expression of human beta-glucuronidase in HepG2 cells.	2003-12	14618298
A nonradioactive 96-well plate assay for screening of trans-sialidase activity.	2003-11-15	14596820
Structural requirements of hydroxylated coumarins for in vitro anti-Helicobacter pylori activity.	2003-11-06	14598616
Pharmacokinetic analysis of factors determining elimination pathways for sulfate and glucuronide metabolites of xenobiotics II: Studies with isolated perfused rat liver.	2003-11	14660174
Inhibition of influenza A virus sialidase activity by sulfatide.	2003-10-23	14572650
Cloning and expression of alpha-D-glucosidase and N-acetyl-beta-glucosaminidase from the periodontal pathogen, Tannerella forsythensis (Bacteroides forsythus).	2003-10	12930523
Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens.	2003-10	12869420
Biochemical and catalytic properties of an endoxylanase purified from the culture filtrate of Sporotrichum thermophile.	2003-09-01	12932372
Enhanced enzymatic hydrolysis of langostino shell chitin with mixtures of enzymes from bacterial and fungal sources.	2003-09-01	12932365
Polar organic solvent added to an aqueous solution changes hydrolytic property of lipase.	2003-08	12951497
Microtiter plate cellular assay for human steroid sulfatase with fluorescence readout.	2003-07-15	12814632
Glucuronidation of 4-methylumbelliferone and 4-hydroxybiphenyl and in vitro induction of UDP-glucuronosyltransferase 2B12-mRNA in precision-cut rat liver slices.	2003-06	12877362
Development of fluorescence-based selective assays for serine/threonine and tyrosine phosphatases.	2003-06	12769677
Detection and characterization of a novel extracellular fungal enzyme that catalyzes the specific and hydrolytic cleavage of lignin guaiacylglycerol beta-aryl ether linkages.	2003-06	12755689
Physicochemical and saccharide-binding studies on the galactose-specific seed lectin from Trichosanthes cucumerina.	2003-05-01	12706350
Solid-phase peptide synthesis by ion-paired alpha-chymotrypsin in nonaqueous media.	2003-03-30	12557314
Highly sensitive active-site titration of lipase in microscale culture media using fluorescent organophosphorus ester.	2003-03-17	12633686
Cloning and characterization of two alpha-glucosidases from Bifidobacterium adolescentis DSM20083.	2003-03	12658515
Kinetic studies on the hydrolysis of N-acetylated and N-deacetylated derivatives of 4-methylumbelliferyl chitobioside by the family 18 chitinases ChiA and ChiB from Serratia marcescens.	2003-02	12761190
A single site in human beta-hexosaminidase A binds both 6-sulfate-groups on hexosamines and the sialic acid moiety of GM2 ganglioside.	2003-01-20	12527415
HNK-1-Reactive oligosaccharide, sulfate-O-3GlcAbeta1-4Xylbeta1-MU, synthesized by cultured human colorectal cancer cells.	2003-01	12688556
Combined polymorphisms in UDP-glucuronosyltransferases 1A1 and 1A6: implications for patients with Gilbert's syndrome.	2003-01	12480553
[Effect of vegetotropic pharmacologic preparations of the motor-evacuatory function of the gallbladder in patients with chronic biliary tract pathology].	2003	12874999
Aryl sulfatase from Naja nigricolis venom: characterization and possible contribution in the pathology of snake poisoning.	2003	12616648
Protection against damaged DNA in the single cell by polyphenols.	2002-12	12561251
Utilization of fluorogenic assay for rapid detection of Escherichia coli in acidic fruit juice.	2002-12	12495014
Optimisation of an enzymatic method for beta-galactosidase.	2002-12	12417103
4-Methylumbelliferone induces the expression of membrane type 1-matrix metalloproteinase in cultured human skin fibroblasts.	2002-11-15	12419303
Some coumarins and triphenylethene derivatives as inhibitors of human testes microsomal 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 3): further studies with tamoxifen on the rat testes microsomal enzyme.	2002-04	12420755
[Effects of 18 alpha-glycyrrhizic acid on rat liver cytochrome P450 isoenzymes and phase II transferase].	2001-05	12584850

Patents

Sample Use Guides

In Vivo Use Guide

1 tablet 3 times daily during basic meals. The tablets are administered unchewed with a liquid.

Route of Administration: Oral

In Vitro Use Guide

4-Methylumbelliferone (4-MU/HYMECROMONE) inhibits hyaluronan synthesis and retards cancer spreading in experimental animals through mechanisms not fully understood. These mechanisms were studied in A2058 melanoma cells, MCF-7 and MDA-MB-361 breast, SKOV-3 ovarian and UT-SCC118 squamous carcinoma cells by analysing hyaluronan synthesis, UDP-glucuronic acid (UDP-GlcUA) content, and hyaluronan synthase (HAS) mRNA levels. The maximal inhibition in hyaluronan synthesis ranged 22-80% in the cell lines tested. Active glucuronidation of 4-MU produced large quantities of 4-MU-glucuronide, depleting the cellular UDP-GlcUA pool. The maximal reduction varied between 38 and 95%. 4-MU also downregulated HAS mRNA levels: HAS3 was 84-60% lower in MDA-MB-361, A2058 and SKOV-3 cells.

Name

Type

Language

HYMECROMONE

Official Name

English

CANTABILINE

Preferred Name

English

HYMECROMONE [MART.]

Common Name

English

HYMECROMONE [JAN]

Common Name

English

4-METHYLUMBELLIFERONE

Common Name

English

LM-94

Code

English

HYMECROMONE [MI]

Common Name

English

NSC-9408

Code

English

2H-1-BENZOPYRAN-2-ONE, 7-HYDROXY-4-METHYL-

Systematic Name

English

7-Hydroxy-4-methylcoumarin

Systematic Name

English

HYMECROMONE [USAN]

Common Name

English

Hymecromone [WHO-DD]

Common Name

English

hymecromone [INN]

Common Name

English

NSC-19026

Code

English

HYMECROMONE [EP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

735220