EDNRB

Summary

EDNRB (endothelin receptor type B, HGNC:3180) is a protein-coding gene on chromosome 13q22.3, encoding Endothelin receptor type B (P24530). Non-specific receptor for endothelin 1, 2, and 3.

The protein encoded by this gene is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three potent vasoactive peptides: ET1, ET2, and ET3. Studies suggest that the multigenic disorder, Hirschsprung disease type 2, is due to mutations in the endothelin receptor type B gene. Alternative splicing and the use of alternative promoters results in multiple transcript variants.

Source: NCBI Gene 1910 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Waardenburg syndrome type 4A (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 364 total — 16 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001122659

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3180
Approved symbol	EDNRB
Name	endothelin receptor type B
Location	13q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ETB
Ensembl gene	ENSG00000136160
Ensembl biotype	protein_coding
OMIM	131244
Entrez	1910

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000377211, ENST00000475537, ENST00000626030, ENST00000643890, ENST00000645696, ENST00000646605, ENST00000646607, ENST00000646948, ENST00000965351

RefSeq mRNA: 4 — MANE Select: NM_001122659 NM_000115, NM_001122659, NM_001201397, NM_003991

CCDS: CCDS45059, CCDS55902, CCDS9461

Canonical transcript exons

ENST00000646607 — 7 exons

Exon	Start	End
ENSE00000923783	77899859	77899967
ENSE00000923784	77900521	77900654
ENSE00000923785	77901058	77901207
ENSE00000923786	77903156	77903360
ENSE00000923787	77903495	77903607
ENSE00003817451	77895487	77898334
ENSE00003817536	77918091	77918831

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.59.

FANTOM5 (CAGE): breadth broad, TPM avg 9.4278 / max 307.2296, expressed in 750 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137698	3.0723	530
137697	2.8606	522
137699	1.1019	440
137703	1.0165	254
137700	0.9119	390
137706	0.1361	38
137702	0.1313	79
137701	0.1109	66
207067	0.0640	26
137705	0.0223	10

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	97.59	gold quality
lateral globus pallidus	UBERON:0002476	96.91	gold quality
lower lobe of lung	UBERON:0008949	96.86	gold quality
superior vestibular nucleus	UBERON:0007227	96.46	gold quality
dorsal root ganglion	UBERON:0000044	96.37	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.02	gold quality
substantia nigra pars compacta	UBERON:0001965	95.76	gold quality
medial globus pallidus	UBERON:0002477	95.66	gold quality
globus pallidus	UBERON:0001875	95.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.48	gold quality
medulla oblongata	UBERON:0001896	95.42	gold quality
right lung	UBERON:0002167	94.98	gold quality
placenta	UBERON:0001987	94.84	gold quality
pericardium	UBERON:0002407	94.84	gold quality
trigeminal ganglion	UBERON:0001675	94.77	gold quality
ventral tegmental area	UBERON:0002691	94.57	gold quality
omental fat pad	UBERON:0010414	94.57	gold quality
peritoneum	UBERON:0002358	94.51	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.45	gold quality
upper lobe of lung	UBERON:0008948	94.32	gold quality
decidua	UBERON:0002450	94.27	gold quality
caudate nucleus	UBERON:0001873	94.24	gold quality
upper lobe of left lung	UBERON:0008952	94.11	gold quality
putamen	UBERON:0001874	94.09	gold quality
lung	UBERON:0002048	93.92	gold quality
nucleus accumbens	UBERON:0001882	93.71	gold quality
subthalamic nucleus	UBERON:0001906	93.67	gold quality
metanephros cortex	UBERON:0010533	93.67	gold quality
adipose tissue	UBERON:0001013	93.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.91	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	1685.87
E-GEOD-135922	yes	1511.29
E-HCAD-56	yes	584.36
E-MTAB-8142	yes	45.02
E-GEOD-93593	yes	14.45
E-CURD-46	yes	12.62
E-MTAB-9388	yes	11.67
E-GEOD-81547	yes	11.43
E-HCAD-1	yes	10.07
E-ENAD-20	no	1426.19
E-MTAB-10137	no	4.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, GATA2, HIF1A, MITF, MTF1, SOX10, SP1

miRNA regulators (miRDB)

163 targeting EDNRB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-651-3P	99.94	73.48	5177

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• novel mutation in a patient with Shah-Waardenburg syndrome and Down syndrome (PMID:11565556)
• The endothelin system plays a role in the complex pathophysiology of idiopathic dilated cardiomyopathy. (PMID:11601839)
• determination of the molecular basis of embryonic arrest from defects associated with mesoderm development (PMID:11829485)
• signal peptide is necessary for translocation of the N-terminal tail across the endoplasmic reticulum membrane. (PMID:11854280)
• A homozygous nonsense mutation in exon 3 (R201X) of the EDNRB gene, a gene known to be involved in Shah-Waardenburg syndrome, was found in ABCD syndrome. (PMID:11891690)
• Repression of endothelin receptor plays a role in the development of nasopharyngeal carcinoma (PMID:11920632)
• The vasoconstrictor effect of endothelin-1 in small resistance arteries of normotensive subjects and, in part, also in hypertensive patients is mediated by ET(A) receptors, while ET(B) receptors play a minor role, if any (PMID:11930911)
• Augmented synthesis and altered expression of ET(B) receptors in the peripheral vasculature contribute to the increased incidence of hypertension and related complications in African American patient populations. (PMID:12117726)
• N-terminal proteolysis has a role in the regulation of cell surface expression of the ET(B) receptor (PMID:12226103)
• genetic interaction between mutations in RET and EDNRB is an underlying mechanism for Hirschsprung disease (PMID:12355085)
• Down-regulation of endothelin receptor B correlated with death from metastatic disease in uveal melanoma (PMID:12439722)
• Detection of endothelin-B receptor gene polymorphisms in patients that have both Hirschsprung’s disease and Down’s syndrome. (PMID:12628594)
• autosomal-dominant polycystic kidney (PMID:12629276)
• a study of interactions with caveolin-1 in caveolae (PMID:12694195)
• Data show that in a human Kaposi sarcoma cell line, blockade of endothelin receptors A and B blocked the endothelin-1-induced increase in secretion and activation of matrix-metalloproteinases. (PMID:12875994)
• The ETB receptor shows remarkable stability in lysosomes, held together by disulfide bonds, and maintaining ligand binding for long periods of time (PMID:12972292)
• ET(B)R is more common in breast carcinomas of patients with lower disease-free survival time and overall survival. (PMID:14519635)
• It is clear from the present data for lung fibroblasts that for both stimulated and unstimulated states of ETB receptors, there exist multiple covalent forms differing in the number and location of sites of posttranslational modifications. (PMID:14636059)
• Mutations are found in Hirschsprung’s disease in a Chinese population. (PMID:14669347)
• Endothelin ETB receptor mRNA levels are significantly higher in arteries from patients with ischemic heart disease as compared to congestive heart failure and controls. (PMID:14729387)
• increased ET-1, ET(A)R, and ET(B)R expression are associated with increased VEGF expression and higher vascularity of breast carcinomas and could be involved in the regulation of angiogenesis in breast cancer (PMID:15073116)
• ET-1/ETA/ETB autocrine/paracrine loops on DCs appear to be essential for the normal maturation and function of human dendritic cells (PMID:15213100)
• Combined cleavage data strongly suggest that the binding domain of ETB receptor includes a portion of the fifth transmembrane domain, between residues Trp275 and Met296. (PMID:15350137)
• Within the second intracellular loop of ETB, a consensus sequence was identified, KXXXVPKXXXV, that is required for ET-1 stimulation of NHE3 activity. (PMID:15598844)
• Endothelin-B receptor blockade inhibits molecular effectors of melanoma cell progression. (PMID:15838263)
• Compared kidney endothelin-A and endothelin-B receptor distribution visualized by radioligand binding versus immunocytochemical localization using subtype selective antisera. (PMID:15838285)
• These data point to ET-1 as a possible survival factor for oligodendrogliomas via ET(B)-R activation and suggest that ET(B)-R-specific antagonists might constitute a potential therapeutic alternative for oligodendrogliomas. (PMID:15950764)
• Polymorphisms in the ET-1 gene (K198N), the ET receptor type A (ETA), (-231G>A and +1222C>T), and the ET type B (ETB) receptor (G57S and L277L) do not play a role in cerebral small-vessel disease (PMID:16002759)
• Inactivation of the EDNRB gene through its promoter methylation is highly prevalent in lung cancer in Taiwan. (PMID:16328051)
• Observations strongly suggest that the expression of ETB receptor is enhanced in neointimal smooth muscle cells at early stages after percutaneous coronary intervention injury in human coronary arteries. (PMID:16531800)
• Reverse transcriptase-polymerase chain reaction analysis revealed mRNA the ETB receptor subtype in the human trigeminal ganglion. Immunocytochemistry revealed numerous cell bodies containing ETB proteins. (PMID:16816835)
• Data show that mutation of EDNRB gene can be detected in Chinese patients with sporadic Hirschsprung’s disease and EDNRB gene might play an important role in the pathogenesis of Hirschsprung’s disease . (PMID:16944573)
• Associations between endothelin receptors A and B in aystemic ssclerosis subsets supports the role of endothelin and its receptors in the pathogenesis of this disease. (PMID:16947775)
• ET receptors in pigment cells of vertebrate species were identified by RT-PCR assays, and the differential expression of the various subtypes in each species was compared by quantitative PCR. (PMID:16962346)
• This study identified additional sequence variants of the EDNRB gene, but the estimated EDNRB haplotypes did not show any disease risk. (PMID:17011274)
• Transfected into mice, implicating endothelin as a major modifying factor for cystic disease progression in human autosomal dominant polycystic kidney disease. (PMID:17202412)
• analysis of Endothelin-1, ETAR and ETBR expression in different histologic subtypes of renal cell carcinoma (PMID:17203161)
• Endogenous endothelin, predominantly via ET(A) receptor stimulation, contributes to basal constrictor tone and endothelial dysfunction, whereas ET(B) activation mediates vasodilation in human coronaries. (PMID:17353514)
• The EDNRB-30G>A polymorphism could be a determinant of airway obstruction in humans with predisposing factors such as tobacco smoke exposure or asthma. (PMID:17470272)
• EDNRB-rs5351 was the most susceptible SNP associated with atherosclerosis in male hypertensives, and the genetic background may be involved in the progression of atherosclerosis in EHT patients. (PMID:17525706)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ednrbb	ENSDARG00000053498
danio_rerio	ednrba	ENSDARG00000089334
mus_musculus	Ednrb	ENSMUSG00000022122
rattus_norvegicus	Ednrb	ENSRNOG00000010997

Paralogs (15): NTSR1 (ENSG00000101188), BRS3 (ENSG00000102239), MLNR (ENSG00000102539), GHSR (ENSG00000121853), GRPR (ENSG00000126010), NMUR2 (ENSG00000132911), NMBR (ENSG00000135577), EDNRA (ENSG00000151617), NTSR2 (ENSG00000169006), GPR37L1 (ENSG00000170075), GPR37 (ENSG00000170775), NMUR1 (ENSG00000171596), GPR148 (ENSG00000173302), TRHR (ENSG00000174417), GPR39 (ENSG00000183840)

Protein

Protein identifiers

Endothelin receptor type B — P24530 (reviewed: P24530)

Alternative names: Endothelin receptor non-selective type

All UniProt accessions (3): A0A2R8Y748, A0A2R8YGF7, P24530

UniProt curated annotations — full annotation on UniProt →

Function. Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in placental stem villi vessels, but not in cultured placental villi smooth muscle cells.

Post-translational modifications. Palmitoylation of Cys-402 was confirmed by the palmitoylation of Cys-402 in a deletion mutant lacking both Cys-403 and Cys-405.

Disease relevance. Waardenburg syndrome 4A (WS4A) [MIM:277580] A disorder characterized by the association of Waardenburg features (depigmentation and deafness) with the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease). The disease is caused by variants affecting the gene represented in this entry. Hirschsprung disease 2 (HSCR2) [MIM:600155] A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. The disease is caused by variants affecting the gene represented in this entry. ABCD syndrome (ABCDS) [MIM:600501] An autosomal recessive syndrome characterized by albinism, black lock at temporal occipital region, bilateral deafness, aganglionosis of the large intestine and total absence of neurocytes and nerve fibers in the small intestine. The disease is caused by variants affecting the gene represented in this entry. Heterozygous mutations in EDNRB may be responsible for Waardenburg syndrome 2, an autosomal dominant disorder characterized by sensorineural deafness and pigmentary disturbances.

Similarity. Belongs to the G-protein coupled receptor 1 family. Endothelin receptor subfamily. EDNRB sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P24530-1	A	yes
P24530-2	B
P24530-3	C, Delta-3

RefSeq proteins (4): NP_000106, NP_001116131, NP_001188326, NP_003982 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000499	Endthln_rcpt	Family
IPR001112	ETB_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR051193	GPCR_endothelin_rcpt	Family

Pfam: PF00001

UniProt features (78 total): sequence variant 18, helix 11, sequence conflict 9, topological domain 8, transmembrane region 7, modified residue 6, strand 5, lipid moiety-binding region 3, mutagenesis site 3, splice variant 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1, disulfide bond 1, turn 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
6IGK	X-RAY DIFFRACTION	2
5X93	X-RAY DIFFRACTION	2.2
5GLI	X-RAY DIFFRACTION	2.5
6IGL	X-RAY DIFFRACTION	2.7
6K1Q	X-RAY DIFFRACTION	2.7
5GLH	X-RAY DIFFRACTION	2.8
8IY5	ELECTRON MICROSCOPY	2.8
8HBD	ELECTRON MICROSCOPY	2.99
6LRY	X-RAY DIFFRACTION	3
8XVE	ELECTRON MICROSCOPY	3
8IY6	ELECTRON MICROSCOPY	3.13
8XGR	ELECTRON MICROSCOPY	3.2
8XWP	ELECTRON MICROSCOPY	3.21
8XVH	ELECTRON MICROSCOPY	3.26
8HCX	ELECTRON MICROSCOPY	3.5
5XPR	X-RAY DIFFRACTION	3.6
8ZRT	ELECTRON MICROSCOPY	3.62
8XWQ	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24530-F1	75.37	0.45

Antibody-complex structures (SAbDab): 8 — 8HBD, 8HCX, 8IY5, 8XGR, 8XVE, 8XVH, 8XWP, 8XWQ

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (9): 305, 419, 439, 440, 441, 442, 402, 403, 405

Disulfide bonds (1): 174–255

Glycosylation sites (1): 59

Mutagenesis-validated functional residues (3):

Position	Phenotype
402	abolishes palmitoylation; when associated with s-403 and s-405.
403	abolishes palmitoylation; when associated with s-402 and s-405.
405	abolishes palmitoylation; when associated with s-402 and s-403.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity

MSigDB gene sets: 537 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, LI_CISPLATIN_RESISTANCE_DN, GOBP_EXCRETION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MATURATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_MYELOID_LEUKOCYTE_MIGRATION

GO Biological Process (59): negative regulation of transcription by RNA polymerase II (GO:0000122), neural crest cell migration (GO:0001755), renin secretion into blood stream (GO:0002001), regulation of heart rate (GO:0002027), regulation of pH (GO:0006885), cell surface receptor signaling pathway (GO:0007166), negative regulation of adenylate cyclase activity (GO:0007194), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), nervous system development (GO:0007399), peripheral nervous system development (GO:0007422), posterior midgut development (GO:0007497), positive regulation of cell population proliferation (GO:0008284), gene expression (GO:0010467), negative regulation of neuron maturation (GO:0014043), vein smooth muscle contraction (GO:0014826), calcium-mediated signaling (GO:0019722), obsolete cGMP-mediated signaling (GO:0019934), heparin proteoglycan metabolic process (GO:0030202), melanocyte differentiation (GO:0030318), regulation of fever generation (GO:0031620), aldosterone metabolic process (GO:0032341), enteric smooth muscle cell differentiation (GO:0035645), positive regulation of urine volume (GO:0035810), renal sodium excretion (GO:0035812), epithelial fluid transport (GO:0042045), vasoconstriction (GO:0042310), vasodilation (GO:0042311), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), developmental pigmentation (GO:0048066), macrophage chemotaxis (GO:0048246), response to pain (GO:0048265), enteric nervous system development (GO:0048484), regulation of epithelial cell proliferation (GO:0050678), negative regulation of protein metabolic process (GO:0051248), canonical Wnt signaling pathway (GO:0060070), positive regulation of penile erection (GO:0060406), establishment of endothelial barrier (GO:0061028), renal sodium ion absorption (GO:0070294)

GO Molecular Function (5): endothelin receptor activity (GO:0004962), peptide hormone binding (GO:0017046), type 1 angiotensin receptor binding (GO:0031702), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), nuclear membrane (GO:0031965), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of biological quality	2
G protein-coupled receptor signaling pathway	2
system development	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
neural crest cell development	1
mesenchymal cell migration	1
renal response to blood flow involved in circulatory renin-angiotensin regulation of systemic arterial blood pressure	1
protein secretion	1
signal release	1
regulation of heart contraction	1
monoatomic cation homeostasis	1
biological regulation	1
signal transduction	1
adenylate cyclase activity	1
negative regulation of catalytic activity	1
regulation of adenylate cyclase activity	1
phospholipase C activator activity	1
nervous system development	1
midgut development	1
anatomical structure development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
macromolecule biosynthetic process	1
regulation of neuron maturation	1
neuron maturation	1
negative regulation of cell maturation	1
phasic smooth muscle contraction	1
vascular associated smooth muscle contraction	1
intracellular signaling cassette	1
proteoglycan metabolic process	1
pigment cell differentiation	1
G protein-coupled peptide receptor activity	1
endothelin receptor signaling pathway	1
hormone binding	1
angiotensin receptor binding	1
transmembrane signaling receptor activity	1
binding	1

Protein interactions and networks

STRING

2346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EDNRB	EDN3	P14138	999
EDNRB	EDN1	P05305	999
EDNRB	EDN2	P20800	998
EDNRB	EDNRA	P25101	943
EDNRB	ECE1	P42892	906
EDNRB	GDNF	P39905	901
EDNRB	SOX10	P56693	901
EDNRB	KITLG	P21583	882
EDNRB	RET	P07949	847
EDNRB	GFRA1	P56159	835
EDNRB	POMC	P01189	752
EDNRB	GNAQ	P50148	744
EDNRB	ECE2	P0DPD6	736
EDNRB	PHOX2B	Q99453	730
EDNRB	KIT	P10721	685

IntAct

15 interactions, top by confidence:

A	B	Type	Score
EDNRB	RARS2	psi-mi:“MI:0915”(physical association)	0.400
EDNRB	EDN1	psi-mi:“MI:0915”(physical association)	0.400
EDN1	EDNRB	psi-mi:“MI:0915”(physical association)	0.400
EDNRB	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
EDNRB	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	EDNRB	psi-mi:“MI:0915”(physical association)	0.400
EDNRB	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
EDNRB	PCNA	psi-mi:“MI:0915”(physical association)	0.370
EDNRB		psi-mi:“MI:0915”(physical association)	0.370
KLRC4	RAP1BL	psi-mi:“MI:0914”(association)	0.350
EDNRB	EXOC5	psi-mi:“MI:0914”(association)	0.350

BioGRID (54): VPS8 (Affinity Capture-MS), C1orf112 (Affinity Capture-MS), LNPEP (Affinity Capture-MS), PXK (Affinity Capture-MS), EXOC2 (Affinity Capture-MS), ATM (Affinity Capture-MS), INTS12 (Affinity Capture-MS), ARFGEF1 (Affinity Capture-MS), KNTC1 (Affinity Capture-MS), THADA (Affinity Capture-MS), TYW1B (Affinity Capture-MS), PDXDC1 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS), KIAA0368 (Affinity Capture-MS), ARFGEF2 (Affinity Capture-MS)

ESM2 similar proteins: A5A4L1, B2ZI34, O08725, O54799, O62709, P14600, P21450, P21451, P21729, P24053, P24530, P25101, P25103, P26684, P28088, P28336, P30547, P30548, P30550, P32304, P32305, P33534, P33535, P34975, P35372, P35463, P41144, P41145, P42866, P47211, P48302, P52500, P56479, P56497, P79350, Q29010, Q2KIP6, Q5DUB3, Q5IS39, Q5IS84

Diamond homologs: A1ZAX0, B2ZI34, E7F7V7, F1MV99, F1R332, O08726, O08786, O43603, O54798, O54799, O62709, O88626, O88854, O97666, O97772, O97967, P05363, P08911, P08912, P21451, P21729, P22270, P24053, P24530, P25101, P26684, P28088, P28336, P28646, P30550, P30551, P30552, P30553, P30796, P30872, P30873, P30937, P30974, P31391, P32238

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
EDN1	up-regulates	EDNRB	binding
EDNRB	“up-regulates activity”	GNAS	binding
EDNRB	“up-regulates activity”	GNAL	binding
EDNRB	“up-regulates activity”	GNAI1	binding
EDNRB	“up-regulates activity”	GNAI3	binding
EDNRB	“up-regulates activity”	GNAO1	binding
EDNRB	“up-regulates activity”	GNAZ	binding
EDNRB	“up-regulates activity”	GNAQ	binding
EDNRB	“up-regulates activity”	GNA14	binding
Endothelin-1	“up-regulates activity”	EDNRB	“chemical activation”
EDN3	up-regulates	EDNRB	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

364 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	17
Uncertain significance	217
Likely benign	70
Benign	13

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1341593	NM_001122659.3(EDNRB):c.1194+1G>C	Pathogenic
147734	GRCh38/hg38 13q22.3-31.3(chr13:77061780-92460406)x1	Pathogenic
148828	GRCh38/hg38 13q14.11-34(chr13:40942298-114340331)x1	Pathogenic
1498840	NM_001122659.3(EDNRB):c.1194+2T>C	Pathogenic
16640	NM_001122659.3(EDNRB):c.601C>T (p.Arg201Ter)	Pathogenic
2004757	NM_001122659.3(EDNRB):c.913del (p.Ser305fs)	Pathogenic
228342	NM_001122659.3(EDNRB):c.618G>A (p.Trp206Ter)	Pathogenic
2710904	NM_001122659.3(EDNRB):c.5del (p.Gln2fs)	Pathogenic
2717861	NM_001122659.3(EDNRB):c.879T>A (p.Tyr293Ter)	Pathogenic
2810375	NM_001122659.3(EDNRB):c.449A>C (p.His150Pro)	Pathogenic
2847500	NM_001122659.3(EDNRB):c.194C>A (p.Ser65Ter)	Pathogenic
3064541	NM_001122659.3(EDNRB):c.292G>T (p.Glu98Ter)	Pathogenic
3655713	NC_000013.11:g.77900653CT[1]	Pathogenic
4710105	NM_001122659.3(EDNRB):c.1008G>A (p.Trp336Ter)	Pathogenic
4729957	NM_001122659.3(EDNRB):c.393C>A (p.Cys131Ter)	Pathogenic
546018	NM_001122659.3(EDNRB):c.306C>A (p.Tyr102Ter)	Pathogenic
1064869	NM_001122659.3(EDNRB):c.777del (p.Val260fs)	Likely pathogenic
1333432	NM_001122659.3(EDNRB):c.801+1G>T	Likely pathogenic
1334125	NM_001122659.3(EDNRB):c.801+2T>C	Likely pathogenic
1510402	NM_001122659.3(EDNRB):c.596+2T>C	Likely pathogenic
2703295	NM_001122659.3(EDNRB):c.802-1G>T	Likely pathogenic
2703346	NM_001122659.3(EDNRB):c.801+2T>A	Likely pathogenic
2706961	NM_001122659.3(EDNRB):c.482A>T (p.Lys161Met)	Likely pathogenic
3039754	NM_001122659.3(EDNRB):c.742A>T (p.Lys248Ter)	Likely pathogenic
3087209	NM_001122659.3(EDNRB):c.87_88dup (p.Gly30fs)	Likely pathogenic
3601071	NM_001122659.3(EDNRB):c.430G>T (p.Ala144Ser)	Likely pathogenic
3601072	NM_001122659.3(EDNRB):c.431C>T (p.Ala144Val)	Likely pathogenic
3906467	NM_001122659.3(EDNRB):c.661G>T (p.Glu221Ter)	Likely pathogenic
425030	NM_001122659.3(EDNRB):c.878dup (p.Tyr293Ter)	Likely pathogenic
444319	NM_001122659.3(EDNRB):c.879dup (p.Thr294fs)	Likely pathogenic

SpliceAI

879 predictions. Top by Δscore:

Variant	Effect	Δscore
13:77901052:TCTTA:T	donor_loss	1.0000
13:77901053:CTTA:C	donor_loss	1.0000
13:77901054:TTA:T	donor_loss	1.0000
13:77901055:TACC:T	donor_loss	1.0000
13:77901056:A:AT	donor_loss	1.0000
13:77901057:CCTG:C	donor_gain	1.0000
13:77901203:TAAAA:T	acceptor_gain	1.0000
13:77901204:AAAA:A	acceptor_gain	1.0000
13:77901205:AAA:A	acceptor_gain	1.0000
13:77901205:AAAC:A	acceptor_loss	1.0000
13:77901206:AA:A	acceptor_gain	1.0000
13:77901206:AACTA:A	acceptor_loss	1.0000
13:77901207:AC:A	acceptor_loss	1.0000
13:77901208:C:CC	acceptor_gain	1.0000
13:77901208:C:T	acceptor_loss	1.0000
13:77901209:T:C	acceptor_loss	1.0000
13:77901210:A:C	acceptor_gain	1.0000
13:77903151:TTTA:T	donor_loss	1.0000
13:77903152:TTAC:T	donor_loss	1.0000
13:77903153:TAC:T	donor_loss	1.0000
13:77903360:TC:T	acceptor_loss	1.0000
13:77903361:C:CA	acceptor_loss	1.0000
13:77903362:T:A	acceptor_loss	1.0000
13:77918086:TTTA:T	donor_loss	1.0000
13:77918087:TTAC:T	donor_loss	1.0000
13:77918088:TACCT:T	donor_loss	1.0000
13:77918089:A:C	donor_loss	1.0000
13:77898335:C:CC	acceptor_gain	0.9900
13:77899968:C:CC	acceptor_gain	0.9900
13:77901056:A:AC	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000001192 (13:77898081 T>A,C), RS1000023905 (13:77974777 G>A), RS1000141148 (13:77953384 C>A), RS1000181776 (13:77950535 TA>T), RS1000238309 (13:77937558 G>T), RS1000241458 (13:77944498 A>C), RS1000289414 (13:77927242 C>G), RS1000317596 (13:77917814 A>G), RS1000393216 (13:77933230 C>A,T), RS1000444083 (13:77933391 G>A,T), RS1000535680 (13:77955042 A>G), RS1000556109 (13:77914435 A>G), RS1000625370 (13:77908933 C>T), RS1000644844 (13:77948737 C>T), RS1000667144 (13:77910537 A>G)

Disease associations

OMIM: gene MIM:131244 | disease phenotypes: MIM:277580, MIM:193500, MIM:600155, MIM:600501, MIM:193510, MIM:617184, MIM:202550, MIM:220290, MIM:607197, MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
Waardenburg syndrome type 4A	Definitive	Autosomal dominant
Waardenburg syndrome type 2	Supportive	Autosomal dominant
Waardenburg-Shah syndrome	Supportive	Autosomal dominant
Hirschsprung disease, susceptibility to, 2	Limited	Unknown

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Waardenburg syndrome type 4A	Limited	AD
Waardenburg syndrome type 4A	Moderate	AR

Mondo (12): Waardenburg syndrome type 4A (MONDO:0010192), Waardenburg syndrome (MONDO:0018094), hearing loss disorder (MONDO:0005365), Hirschsprung disease, susceptibility to, 2 (MONDO:0010833), ABCD syndrome (MONDO:0010895), Waardenburg syndrome type 2A (MONDO:0008671), mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant (MONDO:0014959), aganglionosis, total intestinal (MONDO:0008738), hearing loss, autosomal recessive (MONDO:0019588), Hirschsprung disease (MONDO:0018309), Waardenburg syndrome type 2 (MONDO:0019517), Waardenburg-Shah syndrome (MONDO:0019518)

Orphanet (7): Waardenburg-Shah syndrome (Orphanet:897), Waardenburg syndrome (Orphanet:3440), Hirschsprung disease (Orphanet:388), Rare genetic deafness (Orphanet:96210), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), ABCD syndrome (Orphanet:918)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000077	Abnormality of the kidney
HP:0000365	Hearing impairment
HP:0000366	Abnormality of the nose
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000478	Abnormality of the eye
HP:0000504	Abnormality of vision
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000534	Abnormal eyebrow morphology
HP:0000635	Blue irides
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0001022	Albinism
HP:0001053	Hypopigmented skin patches
HP:0001100	Heterochromia iridis
HP:0001103	Abnormal macular morphology
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001271	Polyneuropathy
HP:0001341	Olfactory lobe agenesis
HP:0001510	Growth delay
HP:0001520	Large for gestational age
HP:0001531	Failure to thrive in infancy
HP:0001561	Polyhydramnios

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000892_9	Total ventricular volume (Alzheimer’s disease interaction)	7.000000e-06
GCST001932_1	Hair color	2.000000e-14
GCST004412_10	Craniofacial microsomia	8.000000e-06
GCST006075_16	Hair color	1.000000e-100
GCST90000025_1053	Appendicular lean mass	2.000000e-35

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003924	hair color
EFO:0004980	appendicular lean mass

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
D014849	Waardenburg Syndrome	C16.131.077.938
C535334	ABCD syndrome (supp.)
C538058	Aganglionosis, total intestinal (supp.)
C564609	Deafness, Autosomal Recessive (supp.)
C536463	Waardenburg syndrome type 2 (supp.)
C536464	Waardenburg syndrome type 2A (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1785 (SINGLE PROTEIN), CHEMBL2096678 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 87,774 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1111	AMBRISENTAN	4	7,009
CHEMBL1373	MODAFINIL	4	14,293
CHEMBL2103873	MACITENTAN	4	1,372
CHEMBL2165326	APROCITENTAN	4	165
CHEMBL282724	SITAXENTAN	4	639
CHEMBL453	SULFISOXAZOLE	4	21,363
CHEMBL781	MAZINDOL	4	16,446
CHEMBL957	BOSENTAN	4	16,499
CHEMBL109648	CLAZOSENTAN	3	244
CHEMBL23261	DARUSENTAN	3	357
CHEMBL3989834	AVOSENTAN	3	364
CHEMBL61780	TEZOSENTAN	3	8,374
CHEMBL9194	ATRASENTAN	3	472
CHEMBL316735	FELOPRENTAN	2	17
CHEMBL431651	ENRASENTAN	2	160
CHEMBL437472	ENDOTHELIN	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Endothelin receptors

Most potent curated ligand interactions (24 total), top 24:

Ligand	Action	Affinity	Parameter
endothelin-3	Full agonist	11.5	pKd
[125I]IRL1620	Full agonist	10.1	pKd
[125I]BQ3020	Full agonist	10.0	pKd
[125I]ET-1 (human, mouse, rat)	Full agonist	10.0	pKd
sarafotoxin S6c	Full agonist	9.8	pKd
[125I][Ala1,3,11,15]ET-1	Full agonist	9.7	pKd
BQ 3020	Full agonist	9.7	pKi
SB209670	Antagonist	9.4	pKB
[Ala1,3,11,15]ET-1	Full agonist	9.2	pKd
sovateltide	Full agonist	8.7	pKi
TAK 044	Antagonist	8.4	pA2
K-8794	Antagonist	8.22	pIC50
A192621	Antagonist	8.1	pKd
BQ788	Antagonist	8.0	pKd
RES7011	Antagonist	8.0	pIC50
Ro 46-8443	Antagonist	7.2	pIC50
IRL 2500	Antagonist	7.2	pKd
bosentan	Antagonist	7.1	pKi
atrasentan	Antagonist	6.86	pKi
clazosentan	Antagonist	6.76	pKi
macitentan	Antagonist	6.41	pIC50
ambrisentan	Antagonist	5.92	pIC50
aprocitentan	Antagonist	5.5	pA2
BMS-193884	Antagonist	4.73	pKi

Binding affinities (BindingDB)

7 measured of 8 human assays (8 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
J-104132	KI	0.1 nM
(1S,2R,3S)-1-Benzo[1,3]dioxol-5-yl-3-(2-carboxymethoxy-4-methoxy-phenyl)-5-propoxy-indan-2-carboxylic acid	KI	21 nM
4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2,2’-bipyrimidin-4-yl]benzenesulfonamide	KI	102 nM
Enrasentan	KI	150 nM
SB-234551	KI	500 nM
SR 147778	KI	1000 nM
PD156707	KI	1420 nM

ChEMBL bioactivities

1034 potent at pChembl≥5 of 1265 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.77	Ki	0.017	nM	ENDOTHELIN 3
10.52	IC50	0.03	nM	ENDOTHELIN 3
10.40	IC50	0.04	nM	ENDOTHELIN 3
10.28	Ki	0.052	nM	ENDOTHELIN 3
10.22	Ki	0.06	nM	ENDOTHELIN
10.04	IC50	0.091	nM	ENDOTHELIN 3
10.00	IC50	0.1	nM	CHEMBL3980643
9.89	IC50	0.13	nM	ENDOTHELIN
9.85	IC50	0.14	nM	CHEMBL325581
9.85	Ki	0.14	nM	CHEMBL310039
9.70	IC50	0.2	nM	CHEMBL419367
9.70	IC50	0.2	nM	ENDOTHELIN
9.68	IC50	0.208	nM	SARAFOTOXIN 6C
9.68	Ki	0.21	nM	CHEMBL433106
9.64	Ki	0.23	nM	CHEMBL72924
9.64	Ki	0.23	nM	CHEMBL308102
9.64	Ki	0.23	nM	CHEMBL305462
9.62	Ki	0.24	nM	CHEMBL306950
9.62	Ki	0.24	nM	CHEMBL72348
9.57	IC50	0.27	nM	CHEMBL339657
9.55	IC50	0.28	nM	CHEMBL111277
9.47	Ki	0.34	nM	CHEMBL310920
9.42	Ki	0.38	nM	CHEMBL73373
9.42	Ki	0.38	nM	CHEMBL73000
9.41	Ki	0.39	nM	CHEMBL307471
9.39	IC50	0.41	nM	CHEMBL1515091
9.33	IC50	0.47	nM	CHEMBL323464
9.32	IC50	0.48	nM	CHEMBL109644
9.31	Ki	0.49	nM	CHEMBL307045
9.30	Ki	0.5	nM	CHEMBL308269
9.23	IC50	0.59	nM	A-192621
9.23	Ki	0.59	nM	CHEMBL307384
9.22	IC50	0.6	nM	CHEMBL323464
9.22	Ki	0.6	nM	CHEMBL307470
9.15	IC50	0.71	nM	CHEMBL332289
9.15	Ki	0.7	nM	CHEMBL73835
9.12	Ki	0.76	nM	CHEMBL70686
9.10	IC50	0.8	nM	A-192621
9.10	IC50	0.8	nM	CHEMBL333972
9.10	IC50	0.8	nM	CHEMBL284250
9.10	Ki	0.79	nM	CHEMBL73697
9.08	IC50	0.83	nM	CHEMBL325581
9.07	IC50	0.85	nM	CHEMBL331625
9.03	IC50	0.94	nM	CHEMBL123316
9.00	Ki	1	nM	CHEMBL72410
8.96	IC50	1.1	nM	CHEMBL331625
8.96	IC50	1.1	nM	CHEMBL73925
8.96	IC50	1.1	nM	CHEMBL330895
8.96	IC50	1.1	nM	CHEMBL332109
8.95	IC50	1.12	nM	CHEMBL109644

PubChem BioAssay actives

834 with measured affinity, of 1842 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-3-[[(2S)-2-[[(2S)-2-[[(1R,4S,7S,10S,13S,16S,19S,22S,25R,28S,31R,36R,39S,42S,45S)-31-amino-7,13-bis(4-aminobutyl)-22,39-dibenzyl-4-(2-carboxyethyl)-10-(carboxymethyl)-19,28-bis[(1R)-1-hydroxyethyl]-16,42-bis[(4-hydroxyphenyl)methyl]-3,6,9,12,15,18,21,24,27,30,38,41,44,47-tetradecaoxo-45-propan-2-yl-33,34,49,50-tetrathia-2,5,8,11,14,17,20,23,26,29,37,40,43,46-tetradecazabicyclo[23.22.4]henpentacontane-36-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1336323: Displacement of [125I]endothelin-1 from human recombinant ETB receptor expressed in CHO cells measured after 120 mins by scintillation counting method	ic50	<0.0001	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(1R,4S,7S,10S,13S,16S,19S,22S,25R,28S,31R,36R,39S,42S,45S)-31-amino-7-(4-aminobutyl)-39-benzyl-4-(2-carboxyethyl)-10-(carboxymethyl)-19,22,28-tris(hydroxymethyl)-42-[(4-hydroxyphenyl)methyl]-16-(1H-indol-3-ylmethyl)-13-(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,38,41,44,47-tetradecaoxo-45-propan-2-yl-33,34,49,50-tetrathia-2,5,8,11,14,17,20,23,26,29,37,40,43,46-tetradecazabicyclo[23.22.4]henpentacontane-36-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1285630: Displacement of [125I]Endothelin-1 from human recombinant Endothelin-B receptor expressed in CHO cells	ic50	<0.0001	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(1S,4S,7S,10R,13S,16R,19S,22R,25R,28R,31S,36R,39S,42R,45S)-31-amino-7,13-bis(4-aminobutyl)-22-benzyl-4-(2-carboxyethyl)-10-(carboxymethyl)-28-[(1R)-1-hydroxyethyl]-19-[(1S)-1-hydroxyethyl]-16-[2-(4-hydroxyphenyl)ethyl]-39,42-bis[(4-hydroxyphenyl)methyl]-3,6,9,12,15,18,21,24,27,30,38,41,44,47-tetradecaoxo-45-propan-2-yl-33,34,49,50-tetrathia-2,5,8,11,14,17,20,23,26,29,37,40,43,46-tetradecazabicyclo[23.22.4]henpentacontane-36-carbonyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	751885: Binding affinity to human ETB receptor by radioligand displacement assay	ki	<0.0001	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[3-chloropropylsulfonyl(propyl)amino]ethyl]-2-(3-fluoro-4-methoxyphenyl)pyrrolidine-3-carboxylic acid	66376: Binding assay performed using human Endothelin B receptor (hETB) expressed in chinese hamster ovary cells(CHO)	ic50	0.0001	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(1R,4S,7S,10S,13S,16S,19S,22S,25R,28S,31R,36R,39S,42S,45S)-31-amino-7-(4-aminobutyl)-39-benzyl-4-(2-carboxyethyl)-10-(carboxymethyl)-19,22,28-tris(hydroxymethyl)-42-[(4-hydroxyphenyl)methyl]-16-(2-methylpropyl)-13-(2-methylsulfanylethyl)-3,6,9,12,15,18,21,24,27,30,38,41,44,47-tetradecaoxo-45-propan-2-yl-33,34,49,50-tetrathia-2,5,8,11,14,17,20,23,26,29,37,40,43,46-tetradecazabicyclo[23.22.4]henpentacontane-36-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1323189: Agonist activity at human recombinant ETB receptor expressed in CHOK1 cells assessed as induction of Ca2+ mobilization by fluorimetric method	ic50	0.0001	uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[(1S,4S,7S,10R,13S,16R,19S,22R,25R,28R,31S,36R,39S,42R,45S)-31-amino-7-(4-aminobutyl)-39-benzyl-4-(2-carboxyethyl)-10-(carboxymethyl)-19,22,28-tris(hydroxymethyl)-42-[(4-hydroxyphenyl)methyl]-16-(2-methylpropyl)-13-(2-methylsulfanylethyl)-3,6,9,12,15,18,21,24,27,30,38,41,44,47-tetradecaoxo-45-propan-2-yl-33,34,49,50-tetrathia-2,5,8,11,14,17,20,23,26,29,37,40,43,46-tetradecazabicyclo[23.22.4]henpentacontane-36-carbonyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	751683: Displacement of [125I]Endothelin-1 from human recombinant ETB receptor expressed in CHOK1 cells after 2 hrs	ki	0.0001	uM
N-[(2R)-1-[[(2S)-1-(ethenylsulfonylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0001	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)-1-[2-[propyl(4,4,4-trifluorobutylsulfonyl)amino]ethyl]pyrrolidine-3-carboxylic acid	66376: Binding assay performed using human Endothelin B receptor (hETB) expressed in chinese hamster ovary cells(CHO)	ic50	0.0002	uM
N-[(2R)-1-[[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(prop-2-enylsulfonylamino)propan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0002	uM
(2S)-2-[[(2R)-2-[(3,5-dimethylbenzoyl)-methylamino]-3-(4-thiophen-3-ylphenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	66852: Binding affinity to Endothelin B receptor	ki	0.0002	uM
(2S)-2-[[(2R)-2-[(3,5-dimethylbenzoyl)-methylamino]-3-[4-(1,2-oxazol-5-yl)phenyl]propanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	66852: Binding affinity to Endothelin B receptor	ki	0.0002	uM
N-[(2R)-1-[[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(propylsulfonylamino)propan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0002	uM
N-[(2R)-1-[[(2S)-1-(2-ethoxyethylsulfonylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0002	uM
N-[(2R)-1-[[(2S)-1-(butylsulfonylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0002	uM
(3S)-3-[[(2S)-5-amino-2-[[(2S)-2-[[(1R,4S,7S,10S,13S,16S,19S,22S,25R,28S,31R,36R,39S,42S,45S)-31-amino-22,42-bis(2-amino-2-oxoethyl)-39-benzyl-4,7-bis(2-carboxyethyl)-10,19-bis(carboxymethyl)-13,28-bis[(1R)-1-hydroxyethyl]-45-(2-methylpropyl)-16-(2-methylsulfanylethyl)-3,6,9,12,15,18,21,24,27,30,38,41,44,47-tetradecaoxo-33,34,49,50-tetrathia-2,5,8,11,14,17,20,23,26,29,37,40,43,46-tetradecazabicyclo[23.22.4]henpentacontane-36-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-5-oxopentanoyl]amino]-4-[[(2S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	699136: Displacement of [I125]ET1 from recombinant ETB receptor expressed in CHO cells after 2 hrs by TopCount analysis	ic50	0.0002	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid	66515: Binding affinity towards human Endothelin B receptor (hET -B)	ic50	0.0003	uM
N-[(2R)-1-[[(2S)-1-(benzenesulfonamido)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0003	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)-1-[2-[pentylsulfonyl(propyl)amino]ethyl]pyrrolidine-3-carboxylic acid	2150548: Antagonist activity at human ETB receptor transfected in CHO cell membrane assessed as inhibition of 125I-labelled ET-3 binding to receptor incubated for 3 hrs by competition binding assay	ic50	0.0003	uM
sodium (2R)-2-[[(2R)-2-[[(2S)-2-[[(2S,6R)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]-3-(1-methoxycarbonylindol-3-yl)propanoyl]amino]hexanoate	1323191: Antagonist activity at ETB receptor in human BSMC assessed as inhibition of endothelin-1 or 3-mediated Ca2+ mobilization preincubated for 5 mins followed by endothelin-1 or 3 addition by fura-2/AM dye-based spectrofluorimetric method	ic50	0.0004	uM
N-[(2R)-1-[[(2S)-3-(1H-indol-3-yl)-1-oxo-1-[[(E)-prop-1-enyl]sulfonylamino]propan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0004	uM
N-[(2R)-1-[[(2S)-3-(1H-indol-3-yl)-1-oxo-1-(propan-2-ylsulfonylamino)propan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0004	uM
N-[(2R)-1-[[(2S)-1-(ethylsulfonylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0004	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[butylsulfonyl(propyl)amino]ethyl]-2-(3-fluoro-4-methoxyphenyl)pyrrolidine-3-carboxylic acid	66376: Binding assay performed using human Endothelin B receptor (hETB) expressed in chinese hamster ovary cells(CHO)	ic50	0.0005	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxyphenyl)-1-[2-[hexylsulfonyl(propyl)amino]ethyl]pyrrolidine-3-carboxylic acid	66376: Binding assay performed using human Endothelin B receptor (hETB) expressed in chinese hamster ovary cells(CHO)	ic50	0.0005	uM
N-[(2R)-1-[[1-(butylsulfonylamino)-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0005	uM
N-[(2R)-1-[[(2S)-1-(benzylsulfonylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0005	uM
N-[(2R)-1-[[1-(butylsulfonylamino)-3-naphthalen-2-yl-1-oxopropan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0006	uM
(2S)-2-[[(2R)-2-[(3,5-dimethylbenzoyl)-methylamino]-3-(4-thiophen-2-ylphenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	66852: Binding affinity to Endothelin B receptor	ki	0.0006	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-(4-propoxyphenyl)pyrrolidine-3-carboxylic acid	2150564: Antagonist activity at human ETB receptor transfected in CHO cell membrane assessed as inhibition of phosphatidylinositol hydrolysis by myo-[3H]inositol radioactivity based assay	ic50	0.0006	uM
N-[(2R)-1-[[1-(butylsulfonylamino)-1-oxobutan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0007	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[(2,2-dimethyl-1-phenylpropyl)amino]-2-oxoethyl]-2-[4-(2-propan-2-yloxyethoxy)phenyl]pyrrolidine-3-carboxylic acid;2,2,2-trifluoroacetic acid	66514: Binding ability determined by the displacement of [125 I]ET-3 from the human Endothelin B receptor	ic50	0.0007	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethyl-4-fluoroanilino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid	66515: Binding affinity towards human Endothelin B receptor (hET -B)	ic50	0.0008	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-[4-(2-methoxyethoxy)phenyl]pyrrolidine-3-carboxylic acid	66515: Binding affinity towards human Endothelin B receptor (hET -B)	ic50	0.0008	uM
(2S)-2-[[(2R)-2-[(3,5-dimethylbenzoyl)-methylamino]-3-[4-(furan-2-yl)phenyl]propanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	66852: Binding affinity to Endothelin B receptor	ki	0.0008	uM
(2S)-2-[[(2R)-2-[(3,5-dimethylbenzoyl)-methylamino]-3-[4-(1,2-oxazol-3-yl)phenyl]propanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	66852: Binding affinity to Endothelin B receptor	ki	0.0008	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[(2,2-dimethyl-1-phenylpropyl)amino]-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid;2,2,2-trifluoroacetic acid	66514: Binding ability determined by the displacement of [125 I]ET-3 from the human Endothelin B receptor	ic50	0.0009	uM
(2S)-2-[[(2R)-2-[(3,5-dimethylbenzoyl)-methylamino]-3-(4-phenylphenyl)propanoyl]amino]-3-(1H-indol-3-yl)propanoic acid	66852: Binding affinity to Endothelin B receptor	ki	0.0010	uM
2-[[(2R)-3-(2-bromo-1H-indol-3-yl)-2-[[2-cyclopropyl-2-[[(2S,6R)-2,6-dimethylpiperidine-1-carbonyl]amino]acetyl]amino]propanoyl]amino]hexanoic acid	66374: Binding affinity towards Endothelin B receptor in human girardi heart cell membranes	ic50	0.0011	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[(2-ethyl-1-phenylbutyl)amino]-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid;2,2,2-trifluoroacetic acid	66514: Binding ability determined by the displacement of [125 I]ET-3 from the human Endothelin B receptor	ic50	0.0011	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[bis(2-methylphenyl)methylamino]-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid;2,2,2-trifluoroacetic acid	66514: Binding ability determined by the displacement of [125 I]ET-3 from the human Endothelin B receptor	ic50	0.0011	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,6-diethylanilino)-2-oxoethyl]-2-(4-ethoxyphenyl)pyrrolidine-3-carboxylic acid	66515: Binding affinity towards human Endothelin B receptor (hET -B)	ic50	0.0012	uM
sodium (2R)-2-[[(2R)-2-[[(2S)-2-[[(2R,6S)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]-3-(1-methoxycarbonylindol-2-yl)propanoyl]amino]hexanoate	1475132: Antagonist activity at ETB receptor (unknown origin) expressed in HEK293T cells measured after 30 mins by CCF4-AM dye based GeneBlazer FRET assay	ic50	0.0012	uM
sodium (2S)-2-[[(2R)-2-[[(2R)-2-[[(2S,6R)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]-3-(1-methoxycarbonylindol-3-yl)propanoyl]amino]hexanoate	1631615: Displacement of [125I]ET-1 from ET-B receptor in human Girardi heart cells incubated for 4 hrs by gamma counting method	ic50	0.0012	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2R,5S,8R,17R)-17-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-4-carboxybutanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-carboxybutanoyl]amino]hexanoyl]amino]-2-[3-(diaminomethylideneamino)propyl]-5-methyl-3,6,14,18-tetraoxo-1,4,7,13-tetrazacyclooctadecane-8-carbonyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-5-[[(2S,3S)-1-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid	66515: Binding affinity towards human Endothelin B receptor (hET -B)	ic50	0.0012	uM
N-[(2R)-1-[[(2S)-1-(butylsulfonylamino)-3-methyl-1-oxobutan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66687: Compound was tested for the binding affinity against Endothelin B receptor	ki	0.0012	uM
N-[(2R)-1-[[1-(butylsulfonylamino)-4-methyl-1-oxopentan-2-yl]amino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-N,3,5-trimethylbenzamide	66852: Binding affinity to Endothelin B receptor	ki	0.0013	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-2-(4-methoxyphenyl)-1-[2-oxo-2-(2,4,6-triethylanilino)ethyl]pyrrolidine-3-carboxylic acid	66515: Binding affinity towards human Endothelin B receptor (hET -B)	ic50	0.0015	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[bis(2-methylphenyl)methylamino]-2-oxoethyl]-2-[4-(2-methoxyethoxy)phenyl]pyrrolidine-3-carboxylic acid;2,2,2-trifluoroacetic acid	66514: Binding ability determined by the displacement of [125 I]ET-3 from the human Endothelin B receptor	ic50	0.0017	uM
(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[bis(2-methylphenyl)methylamino]-2-oxoethyl]-2-[4-(2-propan-2-yloxyethoxy)phenyl]pyrrolidine-3-carboxylic acid;2,2,2-trifluoroacetic acid	66514: Binding ability determined by the displacement of [125 I]ET-3 from the human Endothelin B receptor	ic50	0.0019	uM
N-[3-[6-[(4-tert-butylphenyl)sulfonylamino]-2-cyclopropyl-5-(2-methoxyphenoxy)pyrimidin-4-yl]oxypropyl]thiophene-2-sulfonamide	66539: Inhibitory concentration required against [125I]ET1 binding to membranes of CHO cells expressing human ETB receptor	ic50	0.0020	uM

CTD chemical–gene interactions

77 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	8
bisphenol A	affects cotreatment, increases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Tetrachlorodibenzodioxin	affects reaction, increases expression, affects expression, decreases expression	3
sodium arsenite	decreases reaction, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Arsenic Trioxide	decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Indomethacin	decreases reaction, increases activity, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
lead acetate	increases expression	1
methylselenic acid	increases expression	1
nimesulide	decreases reaction, increases activity	1
mono-(2-ethylhexyl)phthalate	increases expression	1
1,2-dielaidoylphosphatidylethanolamine	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
mercuric bromide	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
paricalcitol	affects cotreatment, affects expression	1
BQ 788	affects binding, decreases activity	1
CGP 52608	affects binding, increases reaction	1
enrasentan	decreases activity, affects binding	1
2-palmitoylglycerol	increases expression	1
rofecoxib	decreases reaction, increases activity	1

ChEMBL screening assays

270 unique, capped per target: 229 binding, 41 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1031404	Binding	Inhibition of human endothelin ETB receptor at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem
CHEMBL1071210	Functional	Agonist activity at ETBR up to 30 uM	The first synthetic agonists of FFA2: Discovery and SAR of phenylacetamides as allosteric modulators. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 3 transformed cell line, 3 cancer cell line, 2 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5PZ	COS-7 1C7	Transformed cell line	Male
CVCL_H427	CHO-K1/EDNRB	Spontaneously immortalized cell line	Female
CVCL_KX00	PathHunter CHO-K1 EDNRB beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA26	PathHunter U2OS EDNRB Total GPCR Internalization	Cancer cell line	Female
CVCL_T419	Psi-CRIP-Rx-ETBR-bsr	Transformed cell line	Male
CVCL_YK44	U2OS EDNRB HiTSeeker	Cancer cell line	Female
CVCL_YK70	U2OS MPX-Nomad ETBR	Cancer cell line	Female
CVCL_YU25	GeneBLAzer EDNRB-NFAT-bla HEK 293T	Transformed cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
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NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
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NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
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NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT02418936	Not specified	UNKNOWN	Development and Clinical Application of Two New Genetic Deafness Gene Diagnostic Kit
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NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
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NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound