ENRASENTAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H30O8
Molecular Weight	506.5437
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCOC1=CC2=C(C=C1)[C@@H]([C@H]([C@@H]2C3=CC=C(OC)C=C3OCCO)C(O)=O)C4=CC=C5OCOC5=C4

InChI

InChIKey=GLCKXJLCYIJMRB-UPRLRBBYSA-N

InChI=1S/C29H30O8/c1-3-11-34-19-6-7-20-22(14-19)27(21-8-5-18(33-2)15-24(21)35-12-10-30)28(29(31)32)26(20)17-4-9-23-25(13-17)37-16-36-23/h4-9,13-15,26-28,30H,3,10-12,16H2,1-2H3,(H,31,32)/t26-,27+,28+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595914
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800004637 | https://www.ncbi.nlm.nih.gov/pubmed/16339819

Enrasentan is an orally active mixed endothelin A/B receptor antagonist with a 100-fold greater affinity for the endothelin A receptor. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan had been in phase II clinical trial for the treatment of heart failure but the results suggested that enrasentan does not appear to have favorable effects on ventricular remodeling.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Endothelin receptor ET-A 19 Target ID: CHEMBL252 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595914	Antagonist 2778		1.1 nM [Ki]
Endothelin receptor ET-B 11 Target ID: CHEMBL1785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595914	Antagonist 2778		111.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Left ventricular systolic dysfunction 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16339819	Primary	Phase II 1132	Unknown Approved Use Unknown
Renal failure 9 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595914 https://www.ncbi.nlm.nih.gov/pubmed/11078416	Primary	Preclinical	Unknown Approved Use Unknown
Pulmonary hypertension 30 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595914 https://www.ncbi.nlm.nih.gov/pubmed/9399985	Primary	Preclinical	Unknown Approved Use Unknown
Stroke 144 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8587428 https://www.ncbi.nlm.nih.gov/pubmed/12595914	Primary	Preclinical	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1L4363
MuseChem	I006676	https://www.musechem.com/product/I006676.html
Smolecule	S527193	http://www.smolecule.com/products/s527193
THE BioTek	bt-267340	https://www.thebiotek.com/product/inhibitors/bt-267340
eNovation Chemicals	D675285	https://www.enovationchem.com/ProductDetails.asp?ProductID=D675285

PubMed

Title	Date	PubMed
Endothelin receptor antagonists.	2006 Jun	16219361

Patents

Sample Use Guides

In Vivo Use Guide

60-90 mg once daily

Route of Administration: Oral

In Vitro Use Guide

The functional activity of enrasentan was evaluated in vitro in rat isolated aorta. In this model enrasentan (10 to 1000 nM) produced concentration-dependent, parallel rightward shifts in the ET-1 concentration-response curve. The Kb value for inhibition of ET-1-induced contraction for enrasentan was 4.4 ± 0.6 nM. The drug was devoid of agonistic activity. In human isolated pulmonary artery enrasentan produced a 7-fold shift to the right of the ET-1 concentration-response curve, with a calculated Kb value of 5.2 nM.

Name

Type

Language

ENRASENTAN

Official Name

English

SB-217242

Code

English

enrasentan [INN]

Common Name

English

(1S,2R,3S)-3-(2-(2-HYDROXYETHOXY)-4-METHOXYPHENYL)-1-(3,4-(METHYLENEDIOXY)PHENYL)-5-PROPOXY-2-INDANCARBOXYLIC ACID

Systematic Name

English

Code System Code Type Description

DRUG BANK

DB06460