Target family: Endothelin receptors (type: gpcr)
Target: ET<sub>A</sub> receptor

Ligand: zibotentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: yes
Median affinity: 8.300000190734863 pIC50
Reference (Journal): Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence.
Published in: Br J Cancer

Ligand: TAK 044 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.399999618530273 pA2
Reference (Journal): Pharmacology of a non-selective ETA and ETB receptor antagonist, TAK-044 and the inhibition of myocardial infarct size in rats.
Published in: Br J Pharmacol

Ligand: [3H]S0139 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 9.199999809265137 pKd
Reference (Journal): Binding characterization of [3H]S-0139, an antagonist of the endothelin ET(A) receptor subtype.
Published in: Eur J Pharmacol

Ligand: [3H]BQ123 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.5 pKd
Reference (Journal): [3H]BQ-123, a highly specific and reversible radioligand for the endothelin ETA receptor subtype.
Published in: Eur J Pharmacol

Ligand: [18F]ET-1 (human, mouse, rat) (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 8.2 pKd
Reference (Journal): (18)F-Endothelin-1, a positron emission tomography (PET) radioligand for the endothelin receptor system: radiosynthesis and in vivo imaging using microPET.
Published in: Clin Sci

Ligand: [125I]sarafotoxin S6b (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Endothelin receptors in human coronary artery and aorta.
Published in: Br J Pharmacol

Ligand: [125I]PD164333 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Characterization of [125I]-PD164333, an ETA selective non-peptide radiolabelled antagonist, in normal and diseased human tissues.
Published in: Br J Pharmacol

Ligand: [125I]PD151242 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pKd
Reference (Journal): [125I]-PD151242: a selective radioligand for human ETA receptors.
Published in: Br J Pharmacol

Ligand: [125I]ET-2 (human) (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Endothelin receptors in human coronary artery and aorta.
Published in: Br J Pharmacol

Ligand: [125I]ET-1 (human, mouse, rat) (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA sub-type.
Published in: Br J Pharmacol

Ligand: [125I]ET-1 (human, mouse, rat) (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney.
Published in: Kidney Int

Ligand: [125I]ET-1 (human, mouse, rat) (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pKd
Reference (Journal): Endothelin receptor density in human hypertrophic and non-hypertrophic prostate tissue.
Published in: Tohoku J Exp Med

Ligand: sparsentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2023)
Primary target: yes
Median affinity: 8.029999732971191 pKi
Reference (Journal): Designed multiple ligands. An emerging drug discovery paradigm.
Published in: J Med Chem

Ligand: sitaxsentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Primary target: yes
Median affinity: 8 pA2
Reference (Journal): Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist.
Published in: J Med Chem

Ligand: SB234551 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): Nonpeptide endothelin receptor antagonists. XI. Pharmacological characterization of SB 234551, a high-affinity and selective nonpeptide ETA receptor antagonist.
Published in: J Pharmacol Exp Ther

Ligand: SB209670 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 9.399999618530273 pKB
Reference (Journal): 1,3-Diarylindan-2-carboxylic acids, potent and selective non-peptide endothelin receptor antagonists.
Published in: J Med Chem

Ligand: sarafotoxin S6b (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro.
Published in: Br J Pharmacol

Ligand: PD164333 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 9 pKd
Reference (Journal): Characterization of [125I]-PD164333, an ETA selective non-peptide radiolabelled antagonist, in normal and diseased human tissues.
Published in: Br J Pharmacol

Ligand: PD-156707 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pKd
Reference (Journal): Affinity and selectivity of PD156707, a novel nonpeptide endothelin antagonist, for human ET(A) and ET(B) receptors.
Published in: J Pharmacol Exp Ther

Ligand: PD-156707 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pA2
Reference (Journal): Affinity and selectivity of PD156707, a novel nonpeptide endothelin antagonist, for human ET(A) and ET(B) receptors.
Published in: J Pharmacol Exp Ther

Ligand: PD-156707 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pA2
Reference (Journal): Blockade and reversal of endothelin-induced constriction in pial arteries from human brain.
Published in: Stroke

Ligand: macitentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA and EMA (2013)
Primary target: yes
Median affinity: 9.300000190734863 pIC50
Reference (Journal): The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist.
Published in: J Med Chem

Ligand: FR139317 (Synthetic organic)
Interaction type: Antagonist
Action: Inverse agonist
Ligand approved: no
Primary target: no
Median affinity:  pIC50
Reference (Journal): ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro.
Published in: Br J Pharmacol

Ligand: endothelin-2 (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity: 8.2 pIC50
Reference (Journal): ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro.
Published in: Br J Pharmacol

Ligand: endothelin-1 (Peptide)
Interaction type: Agonist
Action: Full agonist
Ligand approved: no
Median affinity:  pIC50
Reference (Journal): ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro.
Published in: Br J Pharmacol

Ligand: edonentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 11 pKi
Reference (Journal): Biphenylsulfonamide endothelin receptor antagonists. 4. Discovery of N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]- 2-yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940), a highly potent and orally active ET(A) selective antagonist.
Published in: J Med Chem

Ligand: darusentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Median affinity: 8.9 pKi
Reference (Journal): Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists.
Published in: J Med Chem

Ligand: clazosentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: Japan (2022)
Primary target: no
Median affinity: 9.5 pA2
Reference (Journal): Ro 61-1790, a new hydrosoluble endothelin antagonist: general pharmacology and effects on experimental cerebral vasospasm.
Published in: J Pharmacol Exp Ther

Ligand: clazosentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: Japan (2022)
Primary target: no
Median affinity: 9.890000343322754 pKi
Reference (Journal): Pyrrolidine-3-carboxylic acids as endothelin antagonists. 3. Discovery of a potent, 2-nonaryl, highly selective ETA antagonist (A-216546).
Published in: J Med Chem

Ligand: BQ123 (Peptide)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity:  pA2
Reference (Journal): ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro.
Published in: Br J Pharmacol

Ligand: bosentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2001), EMA (2002)
Primary target: no
Median affinity: 7.199999809265137 pA2
Reference (Journal): Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist.
Published in: J Pharmacol Exp Ther

Ligand: BMS-193884 (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 8.850000381469727 pKi
Reference (Journal): Biphenylsulfonamide endothelin receptor antagonists. 2. Discovery of 4'-oxazolyl biphenylsulfonamides as a new class of potent, highly selective ET(A) antagonists.
Published in: J Med Chem

Ligand: avosentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 7.300000190734863 pIC50
Reference (Patent): Heterocyclic sulfonamides.

Ligand: atrasentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: yes
Median affinity: 10.470000267028809 pKi
Reference (Journal): Pharmacological characterization of A-127722: an orally active and highly potent ETA-selective receptor antagonist.
Published in: J Pharmacol Exp Ther

Ligand: atrasentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: no
Median affinity: 9.199999809265137 pA2
Reference (Journal): Pharmacological characterization of A-127722: an orally active and highly potent ETA-selective receptor antagonist.
Published in: J Pharmacol Exp Ther

Ligand: atrasentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: no
Primary target: yes
Median affinity: 10.470000267028809 pKi
Reference (Journal): 2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
Published in: J Med Chem

Ligand: aprocitentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2024)
Primary target: no
Median affinity: 8.470000267028809 pIC50
Reference (Journal): Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist.
Published in: J Pharmacol Exp Ther

Ligand: aprocitentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2024)
Primary target: no
Median affinity: 6.699999809265137 pA2
Reference (Journal): Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist.
Published in: J Pharmacol Exp Ther

Ligand: ambrisentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2007), EMA (2008)
Primary target: yes
Median affinity: 7.099999904632568 pA2
Reference (Journal): Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists.
Published in: J Med Chem

Ligand: ambrisentan (Synthetic organic)
Interaction type: Antagonist
Action: Antagonist
Ligand approved: yes
Approval source: FDA (2007), EMA (2008)
Primary target: yes
Median affinity: 7.659999847412109 pIC50
Reference (Journal): Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists.
Published in: J Med Chem