PRINABEREL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H10FNO3
Molecular Weight	271.2432
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=CC(C=C)=C2OC(=NC2=C1)C3=CC(F)=C(O)C=C3

InChI

InChIKey=MQIMZDXIAHJKQP-UHFFFAOYSA-N

InChI=1S/C15H10FNO3/c1-2-8-5-10(18)7-12-14(8)20-15(17-12)9-3-4-13(19)11(16)6-9/h2-7,18-19H,1H2

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18097065 | https://www.ncbi.nlm.nih.gov/pubmed/20556817 | https://www.ncbi.nlm.nih.gov/pubmed/14500559

Prinaberel is a selective agonist of estrogen receptor beta. Although initially developed for the treatment of endometriosis, the drug was also shown to be effective in vitro in other inflammatory diseases. Phase II clinical studied revealed its effectiveness in case of Crohn's disease and endometriosis, but the drug failed to demonstrate antiinflammatory efficacy in RA patients.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15456246	Agonist 2678	1216.0 nM [IC50]
Estrogen receptor beta 110 Target ID: CHEMBL242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15456246	Agonist 2678	5.0 nM [IC50]
Estrogen receptor beta 110 Target ID: CHEMBL242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14500559	Agonist 2678	5.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Endometriosis 32 Sources: https://www.clinicaltrials.gov/ct2/show/NCT00110487	Primary	Phase II 1132	Unknown Approved Use Unknown
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20556817	Palliative	Phase II 1132	Unknown Approved Use Unknown
Crohn's disease 42 Sources: https://clinicaltrials.gov/ct2/show/NCT00245947	Palliative	Phase I 428	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20556817 Page: p.1590	unhealthy, ADULT n = 74 Health Status: unhealthy Condition: rheumatoid arthritis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 74 Sources: https://pubmed.ncbi.nlm.nih.gov/20556817 Page: p.1590	Sources: https://pubmed.ncbi.nlm.nih.gov/20556817 Page: p.1590

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681730	inconclusive [IC50 26.837 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681730	yes [IC50 21.3174 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681730	yes [IC50 6.7412 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677934	no

PubMed

Title	Date	PubMed
Evaluation of an estrogen receptor-beta agonist in animal models of human disease.	2003 Oct	14500559
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006 Nov	16497524
Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors.	2014 Oct 1	25106122

Patents

Sample Use Guides

In Vivo Use Guide

In phase II patients received 5, 25, or 75 mg of prinaberel for 12 weeks.

Route of Administration: Oral

In Vitro Use Guide

Human U2OS osteosarcoma cell lines stably expressing a tetracycline regulated ERalpha or beta were treated with 1 ug/ml doxycycline to induce ER expression and then with increasing concentrations of prinaberel (10(-6)-10(-11) M) to test drug effect on proinflammatory genes.

Name

Type

Language

PRINABEREL

Official Name

English

PF-00913086

Code

English

PRINABEREL [USAN]

Common Name

English

7-Ethenyl-2-(3-fluoro-4-hydroxyphenyl)benzoxazol-5-ol

Systematic Name

English

prinaberel [INN]

Common Name

English

ERB-041

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1821