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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 of ENRASENTAN

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

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 TargetPharmacologyConditionPotency
1.1 nM [Ki]
111.0 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

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.