LIAROZOLE FUMARATE

Details

Stereochemistry	RACEMIC
Molecular Formula	2C17H13ClN4.3C4H4O4
Molecular Weight	965.746
Optical Activity	( + / - )
Defined Stereocenters	0 / 2
E/Z Centers	3
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.ClC1=CC=CC(=C1)C(N2C=CN=C2)C3=CC=C4N=CNC4=C3.ClC5=CC=CC(=C5)C(N6C=CN=C6)C7=CC=C8N=CNC8=C7

InChI

InChIKey=IDTXURCCJVODEQ-VQYXCCSOSA-N

InChI=1S/2C17H13ClN4.3C4H4O4/c2*18-14-3-1-2-12(8-14)17(22-7-6-19-11-22)13-4-5-15-16(9-13)21-10-20-15;3*5-3(6)1-2-4(7)8/h2*1-11,17H,(H,20,21);3*1-2H,(H,5,6)(H,7,8)/b;;3*2-1+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1374473 | https://www.ncbi.nlm.nih.gov/pubmed/24102348 | https://www.centerwatch.com/clinical-trials/results/new-therapies/nmt-details.aspx?CatID=279 | https://www.ncbi.nlm.nih.gov/pubmed/16530416

Liarozole is an imidazole-containing compound that inhibits the cytochrome P-450-dependent metabolism of all-trans-retinoic acid (RA). Liarozole, a retinoic acid (RA) metabolism-blocking agent (RAMBA) in clinical development, has been granted orphan drug designation for congenital ichthyosis by the European Commission and the U.S. Food and Drug Administration. Later, based on the mixed results from a phase II/III trial of liarozole for the treatment of ichthyosis, Barrier decided to discontinue the development of liarozole. Liarozole displays antitumor activity against androgen-dependent and independent rat prostate carcinomas.A large phase III international study was completed comparing liarozole 300 mg twice daily with cyproterone acetate (CPA) 100 mg twice daily in a total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy. The results indicate that liarozole might be a possible treatment option for prostate cancer (PCA) following failure of first-line endocrine therapy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 26A1 6 Target ID: CHEMBL5141 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25684424 \| https://www.ncbi.nlm.nih.gov/pubmed/21428449	Inhibitor 8297		540.0 nM [IC50]
Cytochrome P450 19A1 39 Target ID: CHEMBL1978 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20413308	Inhibitor 8297		5.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Ichthyosis 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23870202 https://www.ncbi.nlm.nih.gov/pubmed/19197536	Primary	Phase III 656	Unknown Approved Use Unknown
Prostate cancer 178 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16530416 https://www.ncbi.nlm.nih.gov/pubmed/9671874	Primary	Phase III 656	Unknown Approved Use Unknown
Psoriasis 84 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11703279 https://www.ncbi.nlm.nih.gov/pubmed/11122017 https://www.ncbi.nlm.nih.gov/pubmed/8546999	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3.67 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10763459	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LIAROZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
23.9 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10763459	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		LIAROZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY508247	https://www.001chemical.com/chem/115575-11-6
BOC Sciences	115575-11-6	https://www.bocsci.com/liarozole-cas-115575-11-6-item-258201.html
Clearsynth	CS-L-00027	https://www.clearsynth.com/en/CSL00027.html
Debye Scientific	DA-15205	http://www.debyesci.com/cas_115575-11-6.html
Finetech	FT-0745508	http://www.finetechnology-ind.com/prod/detail/pub/115575-11-6.html
Molcore	MC508247	https://www.molcore.com/product/115575-11-6
MuseChem	M024780	https://www.musechem.com/product/M024780.html
Sigma-Aldrich	SML2040_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/sml2040?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S548671	http://www.smolecule.com/products/s548671
THE BioTek	bt-288074	https://www.thebiotek.com/product/inhibitors/bt-288074
eNovation Chemicals	D604889	https://www.enovationchem.com/ProductDetails.asp?ProductID=D604889
eNovation Chemicals	Y1074231	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y1074231

PubMed

Title	Date	PubMed
Novel tetralone-derived retinoic acid metabolism blocking agents: synthesis and in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays.	2005 Nov 17	16279770
Synthesis and biological evaluation of 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propyl derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26).	2011 Oct 13	21838328

Patents

Sample Use Guides

In Vivo Use Guide

Patients aged ≥ 14 years with moderate/severe lamellar ichthyosis [Investigator's Global Assessment (IGA) score ≥ 3] were randomized 3 : 3 : 1 to receive oral liarozole (75 or 150 mg) or placebo once daily for 12 weeks. Compared with placebo, oral liarozole, 75 or 150 mg, once daily for 12 weeks, reduced the overall severity of ichthyosis and scaling, but not erythema or pruritus, and improved DLQI in patients with moderate or severe lamellar ichthyosis.

Route of Administration: Oral

In Vitro Use Guide

In vitro, liarozole (IC50, 2.2 uM) suppressed the P-450-mediated conversion of RA to more polar metabolites by hamster liver microsomes.

Name

Type

Language

LIAROZOLE FUMARATE

Official Name

English

LIAROZOLE FUMARATE [MI]

Common Name

English

LIAROZOLE FUMARATE [MART.]

Common Name

English

R-85246

Code

English

1H-BENZIMIDAZOLE, 5-((3-CHLOROPHENYL)-1H-IMIDAZOL-1-YLMETHYL)-, (±)-, (E)-2-BUTENEDIOATE (2:3)

Common Name

English

Liarozole fumarate [WHO-DD]

Common Name

English

LIAZAL

Brand Name

English

R 85246

Code

English

(±)-5-(M-CHLORO-.ALPHA.-IMIDAZOL-1-YLBENZYL)BENZIMIDAZOLE FUMARATE (2:3)

Common Name

English

LIAROZOLE FUMARATE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2018