AGTR2

Summary

AGTR2 (angiotensin II receptor type 2, HGNC:338) is a protein-coding gene on chromosome Xq23, encoding Type-2 angiotensin II receptor (P50052). Receptor for angiotensin II, a vasoconstricting peptide.

The protein encoded by this gene belongs to the G-protein coupled receptor 1 family, and functions as a receptor for angiotensin II. It is an intergral membrane protein that is highly expressed in fetus and in neonates, but scantily in adult tissues, except brain, adrenal medulla, and atretic ovary. This receptor has been shown to mediate programmed cell death and this apoptotic function may play an important role in developmental biology and pathophysiology. Mutations in this gene are been associated with X-linked cognitive disability. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and SARS-CoV-2 infection results in down-regulation of angiotensin converting enzyme-2 (ACE2) receptors, the effects of which, triggers serious inflammatory lesions in the tissues involved, primarily in the lungs. The inflammatory reaction appears to be mediated by angiotensin II derivatives, including the angiotensin AT2 receptor which has been found to be upregulated in bronchoalveolar lavage samples from Coronavirus disease 2019 (COVID19) patients.

Source: NCBI Gene 186 — RefSeq curated summary.

At a glance

• Gene–disease (curated): non-syndromic X-linked intellectual disability (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 68 total — 2 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000686

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:338
Approved symbol	AGTR2
Name	angiotensin II receptor type 2
Location	Xq23
Locus type	gene with protein product
Status	Approved
Aliases	AT2, MRX88
Ensembl gene	ENSG00000180772
Ensembl biotype	protein_coding
OMIM	300034
Entrez	186

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000371906, ENST00000680409, ENST00000681852, ENST00000971224

RefSeq mRNA: 2 — MANE Select: NM_000686 NM_000686, NM_001385624

CCDS: CCDS14569

Canonical transcript exons

ENST00000371906 — 3 exons

Exon	Start	End
ENSE00001248880	116170968	116171027
ENSE00001456422	116172246	116174974
ENSE00001456423	116170744	116170816

Expression profiles

Bgee: expression breadth broad, 77 present calls, max score 84.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2250 / max 50.0102, expressed in 33 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197342	0.2250	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	84.02	gold quality
ileal mucosa	UBERON:0000331	70.00	silver quality
smooth muscle tissue	UBERON:0001135	69.64	gold quality
tibia	UBERON:0000979	66.62	silver quality
diaphragm	UBERON:0001103	65.97	gold quality
lower lobe of lung	UBERON:0008949	65.32	silver quality
cartilage tissue	UBERON:0002418	64.86	silver quality
lung	UBERON:0002048	63.57	gold quality
left uterine tube	UBERON:0001303	62.25	gold quality
visceral pleura	UBERON:0002401	62.04	gold quality
right lung	UBERON:0002167	61.79	gold quality
upper lobe of lung	UBERON:0008948	61.04	gold quality
upper lobe of left lung	UBERON:0008952	60.91	gold quality
superficial temporal artery	UBERON:0001614	59.43	silver quality
tibialis anterior	UBERON:0001385	59.09	silver quality
adult organism	UBERON:0007023	57.85	silver quality
pleura	UBERON:0000977	56.64	silver quality
quadriceps femoris	UBERON:0001377	56.62	gold quality
fallopian tube	UBERON:0003889	56.39	gold quality
vastus lateralis	UBERON:0001379	55.70	gold quality
metanephros	UBERON:0000081	54.66	gold quality
endometrium epithelium	UBERON:0004811	53.74	gold quality
deltoid	UBERON:0001476	53.54	gold quality
pancreatic ductal cell	CL:0002079	53.50	silver quality
myometrium	UBERON:0001296	51.95	gold quality
cerebellar vermis	UBERON:0004720	51.73	gold quality
parietal pleura	UBERON:0002400	51.44	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
male germ cell	CL:0000015	50.34	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	48.73
E-ANND-3	yes	3.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF4, ESR1, FOS, IRF1, IRF2, NR1H4, PARP1, SSRP1, TBP, ZBTB16

miRNA regulators (miRDB)

91 targeting AGTR2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4694-3P	99.79	69.53	2640

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• AT(2) receptor overexpression is associated with breast disease, further confirming the involvement of the components of the renin-angiotensin system in the aetiology of breast cancer. (PMID:11819093)
• AT(2) receptor inhibits smooth muscle cell migration via fibronectin cell production and binding. (PMID:11880254)
• AGTR2 mutations in X-linked mental retardation; findings indicate a role for AGTR2 in brain development and cognitive function (PMID:12089445)
• explore the relation among myocardial AT(1)-/AT(2)- receptor expression, myocardial remodeling and cardiac function in patients with congestive heart failure (PMID:12133421)
• There is a potential implication of the AT2G+1675A polymorhism in patient with Left ventricular hypertrophy and coronary ischemia. (PMID:12453540)
• Results support the hypothesis that the DRY motif plays a significant role in the binding affinity, structural stability and G-protein recruiting of the angiotensin II type 2 receptor. (PMID:12531525)
• mRNA levels as well as the protein production of angiotensin II receptors of type 2 was monitored during differentiation of primary human preadipocytes in culture and in mature adipocytes. (PMID:12660887)
• Rare polymorphisms in boys with non-specific mental retardation (PMID:12746399)
• Findings may explain the reported antiangiogenic properties of the AT2 receptor. (PMID:12881481)
• Ang II decreases activity of 11beta-HSD2 by AT2 receptor- and MAPK-dependent mechanism. Decreased activity of 11beta-HSD2 increases intracellular availability of cortisol. May be relevant for pathogenesis of hypertension and preeclampsia. (PMID:12911547)
• This analysis showed that the C4599A polymorphism of the Angiotensin-II type 2 receptor gene was associated with hypertension in women (p=0.0058), but not in men. (PMID:12924622)
• Polymorphisms of the angiotensin II receptor, type 2 gene is associated with increased risk of coronary heart disease in hypertension. (PMID:12925562)
• AGTR2 mutations in male patients is associated with mental retardation (PMID:14598163)
• AT(2) enhances expression of p85 alpha PI3K followed by enhanced p70(S6) kinase (PMID:14657020)
• AT1 and AT2 receptors were found within the epidermis and in dermal vessel walls. (PMID:14987254)
• AT2 receptor-mediated vasodilation in the human heart appears to be limited to coronary microarteries and is mediated by B2 receptors and NO. Most likely, AT2 receptors are located on endothelial cells, and their contribution increases with age. (PMID:15117835)
• Comparison between hypertensive subjects with & w/o left ventricular hypertrophy showed an excess of the G_/GG genotype in the group with LVH. The angiotensin type-2 receptor (-1332 G) allele was associated with LVH in hypertensive subjects. (PMID:15123577)
• Polymorphism is not associated with increased risk of developing chronic kidney allograft dysfunction. (PMID:15385810)
• an imbalance of AT1R and AT2R activity in mesangial cells following exposure to pIgA plays a significant pathogenetic role in the inflammatory injury in IgA nephropathy. (PMID:15458433)
• a major role of the AT2R gene in the development of congenital uropathies has been found, at least in Italian children. (PMID:15470205)
• Increased expression in kidney tubule cells after physical exercise. (PMID:15638358)
• The AT2 receptor regulates expression of genes relevant to cell migration, protein processing, intracellular signaling, and DNA repair in both ligand-dependent and ligand-independent manners. (PMID:15710780)
• The AGTR2 A1675G polymorphism might be involved in the development of essential hypertension in Chinese men. (PMID:16080803)
• Taken together, these data indicate that individuals carrying the G allele may express higher levels of AT2 receptor protein. (PMID:16109806)
• Abundant expression of AT2 receptors in all human fibroblasts studied. (PMID:16112405)
• Sequence variations in AGTR2 are unlikely to be associated with X-linked mental retardation. (PMID:16283672)
• CNK1 binds through the sterile alpha motif (SAM) and the conserved region in CNK (CRIC) to the AT2 receptor. CNK1 may play a role in the AT2 receptor-mediated signaling pathways. (PMID:16289034)
• angiotensin II receptor haplotype transmission is distorted in fetal growth restriction (PMID:16395664)
• AT(1) receptor-mediated activation of PI 3-K/Akt cascades occurs at least partially via the transactivation of EGF receptor, which is under a negative control by AT(2) receptor in hypertrophic scar fibroblasts. (PMID:16522324)
• The ATG2 gene may have a gender-specific efefct on kidney function and pulse pressure in type I diabetic patients. (PMID:16598200)
• There was no significant difference in the distribution of A and G-genotypes in any of the patient groups compared to controls. An A–>1675G transition in the AT2R gene seems not to be involved in the pathogenesis of aortic coarctation. (PMID:16944335)
• Mutations were not detected in the AGTR1 and AGTR2 genes in patients with premature adrenarche; however, two polymorphisms were identified in the AGTR1 gene: the C573T (exon 5) and the A1166C (3’ untranslated region). (PMID:17160213)
• Both AT1 and AT2 receptors were expressed in the fibroblasts of hypertrophic scars, and Ang II regulates DNA synthesis in hypertrophic scar fibroblasts through a negative cross-talk between AT1 and AT2 receptors. (PMID:17393691)
• AT1 an AT2 receptors are developmentally regulated in fetal skin, suggesting theh possible diverse actions that angiotensin II might play in development and maturation of skin (PMID:17433630)
• Data indicate that the angiotensin II type 2 receptor gene A-1332G transition is not associated with the development of human congenital uropathies. (PMID:17515833)
• ANGII signaling occurs primarily via AGTR1 in normal fibroblasts, while AGTR2-mediated effects are dominant on activated (myo)-fibroblasts, a receptor switch that may perturb epithelial-mesenchymal interaction, thereby further perpetuating fibrogenesis. (PMID:17630322)
• Hemizygosity for the G allele was found to be susceptibility factor for hypertension in males (PMID:17707359)
• +1675 G/A angiotensin II type 2 receptor (AT2R) gene polymorphism cannot be considered as a marker of left ventricular hypertrophy in patients with aortic stenosis. (PMID:17944121)
• Although AT2 receptor mRNA is present in human internal mammary arteries, AT2 receptor stimulation does not mediate vasodilation in these arteries. (PMID:18049304)
• Study provides evidence of the expression of the local angiotensin II system in lymph node metastases, and that ACE-, AT1R- and AT2R-activity promotes tumor cell invasion. (PMID:18059164)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	agtr2	ENSDARG00000035552
mus_musculus	Agtr2	ENSMUSG00000068122
rattus_norvegicus	Agtr2	ENSRNOG00000050006

Paralogs (7): BDKRB1 (ENSG00000100739), APLNR (ENSG00000134817), AGTR1 (ENSG00000144891), GPR15 (ENSG00000154165), BDKRB2 (ENSG00000168398), GPR25 (ENSG00000170128), RXFP4 (ENSG00000173080)

Protein

Protein identifiers

Type-2 angiotensin II receptor — P50052 (reviewed: P50052)

Alternative names: Angiotensin II type-2 receptor

All UniProt accessions (1): P50052

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for angiotensin II, a vasoconstricting peptide. Signals primarily via a non-canonical G-protein- and beta-arrestin independent pathways. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation.

Subunit / interactions. Interacts with MTUS1.

Subcellular location. Cell membrane.

Tissue specificity. In adult, highly expressed in myometrium with lower levels in adrenal gland and fallopian tube. Expressed in the cerebellum. Very highly expressed in fetal kidney and intestine.

Domain organisation. Helix VIII may act as a gatekeeper for either suppression or activation of the receptor, depending on post-translational modifications and interactions with various receptor partners. Helix VIII is found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G-proteins or beta-arrestins. Upon switching to a membrane-bound conformation, helix VIII can support the recruitment of G proteins and beta-arrestins.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (2): NP_000677, NP_001372553 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000147	ATII_AT2_rcpt	Family
IPR000248	ATII_rcpt	Family
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (73 total): helix 15, mutagenesis site 11, topological domain 8, transmembrane region 7, binding site 7, sequence variant 6, glycosylation site 5, turn 4, sequence conflict 3, strand 3, disulfide bond 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5UNF	X-RAY DIFFRACTION	2.8
5UNG	X-RAY DIFFRACTION	2.8
5UNH	X-RAY DIFFRACTION	2.9
7JNI	X-RAY DIFFRACTION	3
5XJM	X-RAY DIFFRACTION	3.2
6JOD	X-RAY DIFFRACTION	3.2
7C6A	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50052-F1	82.34	0.58

Antibody-complex structures (SAbDab): 3 — 5XJM, 6JOD, 7C6A

Functional residue map

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

Ligand- & substrate-binding residues (7): 103; 104; 182; 204; 215; 279; 297

Disulfide bonds (2): 35–290, 117–195

Glycosylation sites (5): 4, 13, 24, 29, 34

Mutagenesis-validated functional residues (11):

Position	Phenotype
104	abolished angiotensin ii-binding.
108	abolished angiotensin ii-binding.
128	abolished angiotensin ii-binding.
128	does not affect angiotensin ii-binding.
182	abolished angiotensin ii-binding.
215	abolished angiotensin ii-binding.
269	abolished angiotensin ii-binding.
272	abolished angiotensin ii-binding.
272	does not affect angiotensin ii-binding.
297	abolished angiotensin ii-binding.
308	abolished angiotensin ii-binding.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 245 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, TSENG_IRS1_TARGETS_UP, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_METANEPHROS_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_POSITIVE_REGULATION_OF_KIDNEY_DEVELOPMENT

GO Biological Process (27): blood vessel remodeling (GO:0001974), regulation of systemic arterial blood pressure by circulatory renin-angiotensin (GO:0001991), angiotensin-mediated vasodilation involved in regulation of systemic arterial blood pressure (GO:0002033), brain renin-angiotensin system (GO:0002035), inflammatory response (GO:0006954), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger (GO:0007199), brain development (GO:0007420), regulation of blood pressure (GO:0008217), negative regulation of heart rate (GO:0010459), negative regulation of cell growth (GO:0030308), regulation of metanephros size (GO:0035566), exploration behavior (GO:0035640), nitric oxide-cGMP-mediated signaling (GO:0038060), vasodilation (GO:0042311), negative regulation of blood vessel endothelial cell migration (GO:0043537), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of neurotrophin TRK receptor signaling pathway (GO:0051387), neuron apoptotic process (GO:0051402), positive regulation of metanephric glomerulus development (GO:0072300), positive regulation of branching involved in ureteric bud morphogenesis (GO:0090190), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), signal transduction (GO:0007165), angiotensin-activated signaling pathway (GO:0038166), regulation of apoptotic process (GO:0042981), blood vessel diameter maintenance (GO:0097746)

GO Molecular Function (4): angiotensin type II receptor activity (GO:0004945), receptor antagonist activity (GO:0048019), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
tissue remodeling	1
regulation of systemic arterial blood pressure by renin-angiotensin	1
maintenance of blood vessel diameter homeostasis by renin-angiotensin	1
negative regulation of systemic arterial blood pressure	1
vasodilation	1
nervous system process involved in regulation of systemic arterial blood pressure	1
regulation of blood volume by renin-angiotensin	1
defense response	1
G protein-coupled receptor activity	1
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1
central nervous system development	1
animal organ development	1
head development	1
blood circulation	1
regulation of biological quality	1
regulation of heart rate	1
negative regulation of heart contraction	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
metanephros morphogenesis	1
regulation of kidney size	1
behavior	1
intracellular signaling cassette	1
blood vessel diameter maintenance	1
negative regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
negative regulation of signal transduction	1
neurotrophin TRK receptor signaling pathway	1
regulation of neurotrophin TRK receptor signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
apoptotic process	1
angiotensin receptor activity	1
signaling receptor binding	1

Protein interactions and networks

STRING

1845 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGTR2	AGT	P01019	999
AGTR2	ACE2	Q9BYF1	953
AGTR2	ACE	P12821	949
AGTR2	REN	P00797	934
AGTR2	AGTR1	P30556	835
AGTR2	MTUS1	Q9ULD2	826
AGTR2	TIMP3	P35625	801
AGTR2	KNG1	P01042	777
AGTR2	TMPRSS2	O15393	667
AGTR2	STOX1	Q6ZVD7	599
AGTR2	SFTPC	P11686	594
AGTR2	EDN1	P05305	593
AGTR2	BSG	P35613	588
AGTR2	DPP4	P27487	575
AGTR2	ATP6AP2	O75787	565

IntAct

17 interactions, top by confidence:

A	B	Type	Score
TIMP3	AGTR2	psi-mi:“MI:0915”(physical association)	0.580
AGTR2	TIMP3	psi-mi:“MI:0915”(physical association)	0.580
AGTR2	AGT	psi-mi:“MI:0407”(direct interaction)	0.440
AGTR2	AGT	psi-mi:“MI:0915”(physical association)	0.400
AGT	AGTR2	psi-mi:“MI:0915”(physical association)	0.400
AGTR2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	AGTR2	psi-mi:“MI:0915”(physical association)	0.400
AGTR2	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	AGTR2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (16): AGTR2 (Reconstituted Complex), MTUS1 (Two-hybrid), MTUS1 (Affinity Capture-Western), AGTR2 (Affinity Capture-MS), AGTR2 (Two-hybrid), AGTR2 (Co-localization), AGTRAP (Reconstituted Complex), AGTR2 (FRET), ACE2 (FRET), AGTR2 (Protein-peptide), AGTR2 (Protein-peptide), AGTR2 (Two-hybrid), AGTR2 (Affinity Capture-Western), TIMP3 (Affinity Capture-Western), AGTR2 (Dosage Lethality)

ESM2 similar proteins: A1A5S3, A5PLE7, B0UXR0, B5X337, F5HDK1, F5HF62, F8VQN3, O00421, O18982, O97663, P09703, P32249, P35351, P35374, P46002, P49685, P50052, P51676, P56412, P69332, P69333, Q01035, Q0II78, Q0VDU3, Q14330, Q1RMI1, Q28929, Q3T0E9, Q3U507, Q4R613, Q6IYF9, Q75ZH0, Q83207, Q89609, Q8BZR0, Q8IYL9, Q8K1Z6, Q95N03, Q96P67, Q98146

Diamond homologs: A0T2N3, F1MV99, O00155, O00590, O08707, O08858, O09027, O35210, O77590, O88410, O89039, O97666, P0C5I1, P0C7U4, P11613, P21109, P25024, P25025, P25095, P25104, P25106, P29089, P29754, P29755, P30555, P30556, P30680, P30874, P30875, P30935, P30936, P30937, P30938, P31391, P32303, P32745, P33396, P33535, P34976, P34993

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
AGTR2	up-regulates	GNAQ	binding
AGT	up-regulates	AGTR2
AGTR2	up-regulates	Apoptosis
Angiotensin-2	“up-regulates activity”	AGTR2	binding
AGTR2	down-regulates	Angiogenesis
CGP-42112A	“down-regulates activity”	AGTR2	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	47
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2685761	GRCh37/hg19 Xq23-25(chrX:110921170-124327177)x2	Pathogenic
3246674	NC_000023.10:g.(?113818282)(115590299_?)del	Pathogenic
150133	GRCh38/hg38 Xq23(chrX:112920714-116408703)x0	Likely pathogenic
442292	GRCh37/hg19 Xq23-24(chrX:111149921-117993284)x3	Likely pathogenic

SpliceAI

319 predictions. Top by Δscore:

Variant	Effect	Δscore
X:116170812:TGAAG:T	donor_gain	1.0000
X:116170813:GAAG:G	donor_gain	1.0000
X:116170813:GAAGG:G	donor_gain	1.0000
X:116170814:AAG:A	donor_gain	1.0000
X:116170815:AG:A	donor_gain	1.0000
X:116170816:GG:G	donor_gain	1.0000
X:116170817:G:GG	donor_gain	1.0000
X:116170817:GT:G	donor_loss	1.0000
X:116171360:A:G	donor_gain	1.0000
X:116172245:GAA:G	acceptor_gain	1.0000
X:116171028:G:GG	donor_gain	0.9900
X:116172244:A:AG	acceptor_gain	0.9900
X:116172245:G:GG	acceptor_gain	0.9900
X:116172402:A:G	donor_gain	0.9900
X:116172240:CCACA:C	acceptor_loss	0.9800
X:116172241:CACAG:C	acceptor_loss	0.9800
X:116172243:CAG:C	acceptor_loss	0.9800
X:116172244:AGA:A	acceptor_loss	0.9800
X:116172245:G:GT	acceptor_loss	0.9800
X:116172245:GA:G	acceptor_gain	0.9800
X:116171024:ACCA:A	donor_gain	0.9700
X:116172244:AGAAG:A	acceptor_gain	0.9700
X:116172245:GAAGG:G	acceptor_gain	0.9700
X:116170967:GGA:G	acceptor_gain	0.9600
X:116170967:GGAGT:G	acceptor_gain	0.9600
X:116171025:CCA:C	donor_gain	0.9600
X:116171359:GA:G	donor_gain	0.9600
X:116171026:CAGT:C	donor_loss	0.9500
X:116171027:AGT:A	donor_loss	0.9500
X:116171029:T:G	donor_loss	0.9500

AlphaMissense

2397 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:116172825:G:C	R182P	0.999
X:116172549:A:C	D90A	0.998
X:116172610:G:C	W110C	0.998
X:116172610:G:T	W110C	0.998
X:116172863:T:A	C195S	0.998
X:116172864:G:A	C195Y	0.998
X:116172864:G:C	C195S	0.998
X:116172865:C:G	C195W	0.998
X:116173073:T:C	F265L	0.998
X:116173075:C:A	F265L	0.998
X:116173075:C:G	F265L	0.998
X:116172549:A:T	D90V	0.997
X:116172608:T:A	W110R	0.997
X:116172608:T:C	W110R	0.997
X:116172629:T:A	C117S	0.997
X:116172630:G:C	C117S	0.997
X:116172695:A:C	S139R	0.997
X:116172697:T:A	S139R	0.997
X:116172697:T:G	S139R	0.997
X:116172863:T:C	C195R	0.997
X:116172935:G:C	G219R	0.997
X:116172452:G:A	G58R	0.996
X:116172452:G:C	G58R	0.996
X:116172549:A:G	D90G	0.996
X:116172573:C:G	P98R	0.996
X:116172630:G:A	C117Y	0.996
X:116172631:C:G	C117W	0.996
X:116172671:A:C	S131R	0.996
X:116172673:C:A	S131R	0.996
X:116172673:C:G	S131R	0.996

dbSNP variants (sampled 300 via entrez): RS1001070750 (X:116172158 G>C,T), RS1004547052 (X:116171525 A>T), RS1005810879 (X:116169187 A>C), RS1006647620 (X:116174598 A>C), RS1007111173 (X:116174081 T>C), RS1008731705 (X:116172112 A>G), RS1010718452 (X:116175443 G>A), RS1010772248 (X:116175119 C>T), RS1015898794 (X:116169232 A>G), RS1016888863 (X:116171553 G>A), RS1017003125 (X:116170771 C>T), RS1017365861 (X:116171194 G>A), RS1019816022 (X:116174622 A>C), RS1020122380 (X:116169449 T>C), RS1021548248 (X:116171716 T>G)

Disease associations

OMIM: gene MIM:300034 | disease phenotypes: MIM:300852

GenCC curated gene-disease

Disease	Classification	Inheritance
non-syndromic X-linked intellectual disability	Supportive	X-linked
X-linked complex neurodevelopmental disorder	Limited	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Disputed	XL

Mondo (3): intellectual disability, X-linked 88 (MONDO:0010454), non-syndromic X-linked intellectual disability (MONDO:0019181), X-linked complex neurodevelopmental disorder (MONDO:0100148)

Orphanet (1): X-linked non-syndromic intellectual disability (Orphanet:777)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001077_2	Cystic fibrosis severity	2.000000e-06
GCST003143_1	Lung disease severity in cystic fibrosis	5.000000e-10
GCST003143_2	Lung disease severity in cystic fibrosis	5.000000e-08
GCST003143_3	Lung disease severity in cystic fibrosis	1.000000e-09
GCST003143_4	Lung disease severity in cystic fibrosis	5.000000e-06
GCST003143_5	Lung disease severity in cystic fibrosis	3.000000e-08
GCST003143_6	Lung disease severity in cystic fibrosis	9.000000e-06
GCST004898_4	Preterm birth (maternal effect)	1.000000e-11
GCST004899_1	Gestational age at birth (maternal effect)	7.000000e-16
GCST005898_1	Type 2 diabetes	8.000000e-09
GCST006484_2	Type 2 diabetes	1.000000e-09
GCST008363_13	Offspring birth weight	2.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007744	lung disease severity measurement
EFO:0003917	premature birth
EFO:0005939	parental genotype effect measurement
EFO:0005112	gestational age
EFO:0004344	birth weight

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094256 (PROTEIN FAMILY), CHEMBL4607 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 529,684 (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
CHEMBL1513	IRBESARTAN	4	31,667
CHEMBL191	LOSARTAN	4	88,932
CHEMBL938	SARALASIN	4	7,408
CHEMBL995	LOSARTAN POTASSIUM	4	11,860
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL1200692	OLMESARTAN MEDOXOMIL	4	17,268
CHEMBL139	DICLOFENAC	4	125,009
CHEMBL2028661	AZILSARTAN MEDOXOMIL	4	450
CHEMBL408403	ANGIOTENSIN II	4	76,759
CHEMBL838	BENAZEPRIL	4	28,085
CHEMBL91	MICONAZOLE	4	45,914
CHEMBL1016	CANDESARTAN	3	37,149
CHEMBL1516	OLMESARTAN	3	359
CHEMBL2391146	ANGIOTENSIN	3	703
CHEMBL315021	FORASARTAN	2	2,597
CHEMBL41194	PRATOSARTAN	2	1,926
CHEMBL432162	TASOSARTAN	2	14,728
CHEMBL34124	OLODANRIGAN	2	219

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Angiotensin receptors

Most potent curated ligand interactions (16 total), top 16:

Ligand	Action	Affinity	Parameter
[125I]CGP42112	Full agonist	10.6	pKd
angiotensin III	Full agonist	10.4	pKd
angiotensin II	Full agonist	10.2	pKd
CGP42112	Full agonist	9.63	pIC50
PD123177	Antagonist	9.49	pIC50
compound 1 [PMID: 28379944]	Antagonist	9.47	pKi
compound 2 [PMID: 28379944]	Antagonist	9.46	pKi
[p-aminoPhe6]ang II	Full agonist	9.41	pKd
compound 21 [PMID: 22802221]	Agonist	9.4	pKi
PD123319	Antagonist	9.2	pKd
saralasin	Antagonist	9.0	pIC50
[125I][Sar1,Ile8]Ang-II	Full agonist	8.77	pKd
angiotensin A	Agonist	8.64	pKi
novokinin	Agonist	8.13	pKi
olodanrigan	Antagonist	7.4	pKd
angiotensin-(1-7)	Agonist	6.61	pIC50

Binding affinities (BindingDB)

192 measured of 194 human assays (194 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[3-[2-methyl-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonyl-3-(pyridin-2-ylmethyl)urea	IC50	1 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[4-[(2-ethylimidazol-1-yl)methyl]phenyl]-4-methyl-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	1.32 nM	US-20250214978: AT2R AGONIST
butyl N-[3-[3-cyano-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	1.35 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[2-methyl-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	1.51 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[3-cyano-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	1.51 nM	US-20250214978: AT2R AGONIST
methyl N-[4-methyl-5-(2-methylpropyl)-3-[4-[(2-propan-2-ylimidazol-1-yl)methyl]phenyl]thiophen-2-yl]sulfonylcarbamate	IC50	1.61 nM	US-20250214978: AT2R AGONIST
1-[3-[2-cyano-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonyl-3-(3,3,3-trifluoropropyl)urea	IC50	1.63 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[3-cyano-4-[(2-ethylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	1.68 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[4-[(2-tert-butylimidazol-1-yl)methyl]-3-cyanophenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	1.72 nM	US-20250214978: AT2R AGONIST
2-[[1-[2-[[2-[[2-[[2-[[5-(diaminomethylideneamino)-2-[(2,4-diamino-4-oxobutanoyl)amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid	IC50	1.8 nM	US-10370388: Heterocyclic compounds and methods of their use
L-alpha-aspartyl-L-arginyl-L-valyl-L-tyrosyl-L-isoleucyl-L-histidyl-L-prolyl-L-phenylalanine	IC50	1.8 nM	US-9624243: Heterocyclic compounds and methods of their use
methyl N-[3-[4-[(2-tert-butylimidazol-1-yl)methyl]-2-cyanophenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	2.09 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[2-cyano-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	2.15 nM	US-20250214978: AT2R AGONIST
butyl N-[3-[2-methyl-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	2.39 nM	US-20250214978: AT2R AGONIST
methyl N-[4-methyl-3-[4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	2.68 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[3-methyl-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	2.73 nM	US-20250214978: AT2R AGONIST
butyl N-[3-[4-(imidazol-1-ylmethyl)-3-methylphenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	3.32 nM	US-20250214978: AT2R AGONIST
US20250214978, Compound I-27	IC50	3.35 nM	US-20250214978: AT2R AGONIST
methyl N-[4-methyl-3-[3-methyl-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	3.4 nM	US-20250214978: AT2R AGONIST
1-[(2S,4S)-4-[3-(4-fluorophenyl)propyl-methylamino]-2-(tetrazolidin-5-yl)pyrrolidin-1-yl]-2,2-diphenylethanone	IC50	3.52 nM	US-9624243: Heterocyclic compounds and methods of their use
1-[(4S)-4-[3-(4-fluorophenyl)propyl-methylamino]-2-(2H-tetrazol-5-yl)pyrrolidin-1-yl]-2,2-diphenylethanone	IC50	3.52 nM	US-10370388: Heterocyclic compounds and methods of their use
butyl N-[3-[3-cyano-4-(imidazol-1-ylmethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	3.54 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[2-methyl-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	3.76 nM	US-20250214978: AT2R AGONIST
butyl N-[3-[4-(1-imidazol-1-ylethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	3.8 nM	US-20250214978: AT2R AGONIST
butyl N-[3-[2-cyano-4-(imidazol-1-ylmethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	3.95 nM	US-20250214978: AT2R AGONIST
ethyl N-[4-methyl-3-[4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	4.06 nM	US-20250214978: AT2R AGONIST
butyl N-[3-[4-(imidazol-1-ylmethyl)-2-methylphenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	4.28 nM	US-20250214978: AT2R AGONIST
methyl N-[3-[4-[(2-chloroimidazol-1-yl)methyl]phenyl]-4-methyl-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	4.32 nM	US-20250214978: AT2R AGONIST
butyl N-[3-[4-(imidazol-1-ylmethyl)phenyl]-4-methyl-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	4.4 nM	US-20250214978: AT2R AGONIST
propyl N-[4-methyl-3-[4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	4.5 nM	US-20250214978: AT2R AGONIST
butyl N-[4-methyl-3-[4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	4.86 nM	US-20250214978: AT2R AGONIST
US20250214978, Compound I-25	IC50	5.65 nM	US-20250214978: AT2R AGONIST
methyl (2S,4R)-4-(7,8-difluoro-3,4-dihydro-2H-1,5-benzoxazepin-5-yl)-1-(2,2-diphenylacetyl)piperidine-2-carboxylate	KI	7 nM	US-10308628: Heterocyclic compounds and methods for their use
1-ethyl-3-[3-[3-methyl-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylurea	IC50	7.28 nM	US-20250214978: AT2R AGONIST
(2S,4R)-1-(2,2-diphenylacetyl)-4-(8-fluoro-3,4-dihydro-2H-1,5-benzoxazepin-5-yl)piperidine-2-carboxylic acid	KI	9 nM	US-10308628: Heterocyclic compounds and methods for their use
(2S,4R)-1-(2,2-diphenylacetyl)-4-(7-methoxy-2,3,4,5-tetrahydro-1-benzazepin-1-yl)piperidine-2-carboxylic acid	KI	9 nM	US-10308628: Heterocyclic compounds and methods for their use
(3S)-N-(dimethylsulfamoyl)-2-(2,2-diphenylacetyl)-6-methoxy-5-phenylmethoxy-3,4-dihydro-1H-isoquinoline-3-carboxamide	IC50	10.9 nM	US-9714224: Heterocyclic compounds and methods of their use
(1R,2S,5S)-3-(diphenylcarbamoyl)-8-[1H-indol-6-ylmethyl(methyl)carbamoyl]-3,8-diazabicyclo[3.2.1]octane-2-carboxylic acid	IC50	10.9 nM	US-11453690: Receptor inhibitor, pharmaceutical composition comprising same, and use thereof
Losartan	IC50	11 nM	US-10370388: Heterocyclic compounds and methods of their use
1-(2-hydroxyethyl)-3-[3-[3-methyl-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylurea	IC50	11.3 nM	US-20250214978: AT2R AGONIST
butyl N-[3-[6-(imidazol-1-ylmethyl)-3-pyridinyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	IC50	11.4 nM	US-20250214978: AT2R AGONIST
(2S,4S)-1-(2,2-diphenylacetyl)-4-((3-(4-fluorophenyl)-propyl)(methyl)amino)pyrrolidine-2-carboxylic acid	IC50	12 nM	US-10370388: Heterocyclic compounds and methods of their use
(2S,4R)-4-(3,4-dihydro-2H-1,5-benzoxazepin-5-yl)-1-(2,2-diphenylacetyl)piperidine-2-carboxylic acid	KI	15 nM	US-10308628: Heterocyclic compounds and methods for their use
(2S,4R)-1-(2,2-diphenylacetyl)-4-(7-fluoro-3,4-dihydro-2H-1,5-benzoxazepin-5-yl)piperidine-2-carboxylic acid	KI	17 nM	US-10308628: Heterocyclic compounds and methods for their use
1-[3-[[(1S,3R)-3-[1-(dimethylsulfamoylamino)ethenyl]-4-(2,2-diphenylacetyl)cyclopentyl]-methylamino]propyl]-4-fluorobenzene	IC50	17.1 nM	US-9624243: Heterocyclic compounds and methods of their use
(2R,4R)-N-(dimethylsulfamoyl)-1-(2,2-diphenylacetyl)-4-[3-(4-fluorophenyl)propyl-methylamino]pyrrolidine-2-carboxamide	IC50	17.1 nM	US-10370388: Heterocyclic compounds and methods of their use
(2S,4S)-1-(2,2-diphenylacetyl)-4-(5-phenyl-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxylic acid	IC50	18 nM	US-10370388: Heterocyclic compounds and methods of their use
(2S,4S)-1-(2,2-diphenylacetyl)-4-[2-(2-fluorophenoxy)ethyl-methylamino]pyrrolidine-2-carboxylic acid	IC50	20.5 nM	US-10370388: Heterocyclic compounds and methods of their use
(2S,4S)-1-(2,2-diphenylacetyl)-4-(8-fluoro-2,3,4,5-tetrahydro-1-benzazepin-1-yl)piperidine-2-carboxylic acid	KI	21 nM	US-10308628: Heterocyclic compounds and methods for their use
(2S,4R)-1-(2,2-diphenylacetyl)-4-(8-fluoro-2,3,4,5-tetrahydro-1-benzazepin-1-yl)piperidine-2-carboxylic acid	KI	23 nM	US-10308628: Heterocyclic compounds and methods for their use

ChEMBL bioactivities

1453 potent at pChembl≥5 of 1473 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.90	Kd	0.01259	nM	CHEMBL47177
10.70	Kd	0.01995	nM	CHEMBL416477
10.33	Kd	0.04677	nM	CHEMBL125218
10.30	Kd	0.05012	nM	CHEMBL293511
10.30	Kd	0.05012	nM	CHEMBL418226
10.25	Kd	0.05623	nM	CHEMBL92542
10.18	IC50	0.066	nM	SARALASIN
10.10	Kd	0.07943	nM	CHEMBL416477
10.10	Ki	0.08	nM	CHEMBL1791308
10.10	IC50	0.08	nM	CHEMBL385433
10.10	IC50	0.08	nM	ANGIOTENSIN II
10.10	IC50	0.08	nM	CHEMBL295854
10.09	Kd	0.08128	nM	CARBOXYLIC ACID METABOLITE
10.04	Kd	0.0912	nM	PRATOSARTAN
10.01	Kd	0.09772	nM	PRATOSARTAN
10.00	IC50	0.1	nM	L-158809
10.00	IC50	0.1	nM	CHEMBL42775
10.00	IC50	0.1	nM	CHEMBL298417
9.96	Ki	0.11	nM	ANGIOTENSIN-II
9.92	IC50	0.12	nM	CHEMBL338027
9.89	IC50	0.13	nM	ANGIOTENSIN
9.85	Ki	0.14	nM	CHEMBL404594
9.82	Ki	0.15	nM	SARALASIN
9.80	Kd	0.1585	nM	CHEMBL313371
9.80	Kd	0.1585	nM	CHEMBL44295
9.80	Kd	0.1585	nM	CHEMBL289391
9.74	Ki	0.18	nM	CHEMBL216061
9.71	Kd	0.195	nM	CARBOXYLIC ACID METABOLITE
9.70	Kd	0.1995	nM	CHEMBL88411
9.70	Kd	0.1995	nM	CHEMBL387040
9.70	Ki	0.2	nM	ANGIOTENSIN II
9.70	IC50	0.2	nM	CHEMBL2369937
9.70	IC50	0.2	nM	L-158809
9.70	IC50	0.2	nM	CHEMBL43424
9.70	IC50	0.2	nM	CHEMBL288246
9.70	IC50	0.2	nM	CHEMBL43535
9.70	IC50	0.2	nM	CHEMBL43500
9.69	Kd	0.2042	nM	CHEMBL315728
9.68	Kd	0.2089	nM	CHEMBL49410
9.68	IC50	0.21	nM	ANGIOTENSIN-II
9.68	IC50	0.21	nM	CHEMBL404594
9.66	Kd	0.2188	nM	CHEMBL40340
9.66	Kd	0.2188	nM	CHEMBL43540
9.64	Kd	0.2291	nM	CHEMBL91255
9.64	Ki	0.23	nM	ANGIOTENSIN II
9.64	Kd	0.2291	nM	CHEMBL43530
9.63	Kd	0.2344	nM	CHEMBL92062
9.63	Kd	0.2344	nM	L-158809
9.60	Kd	0.2512	nM	CHEMBL421473
9.57	Kd	0.2692	nM	CHEMBL1237157

PubChem BioAssay actives

722 with measured affinity, of 1359 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
6-[(2S,3aR)-2-methyl-3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-b][1,2]oxazol-2-yl]-2-butyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]quinazolin-4-one	167381: Inhibition of angiotensin II-induced contractions in rabbit aorta in vitro.	kd	<0.0001	uM
2-[propyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyridine-3-carboxylic acid	167381: Inhibition of angiotensin II-induced contractions in rabbit aorta in vitro.	kd	<0.0001	uM
2-[butyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyridine-3-carboxylic acid	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	<0.0001	uM
N,N-dimethyl-2-[4-oxo-2-propyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]acetamide	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0001	uM
(2S,3S)-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoic acid	1169023: Binding affinity to AT2 receptor (unknown origin)	ki	0.0001	uM
N-tert-butyl-2-[2-butyl-4-oxo-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]acetamide	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0001	uM
2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylic acid	167381: Inhibition of angiotensin II-induced contractions in rabbit aorta in vitro.	kd	0.0001	uM
N-[2-[4-[(2-ethyl-5,7-dimethylimidazo[4,5-b]pyridin-3-yl)methyl]phenyl]phenyl]sulfonylbenzamide	167381: Inhibition of angiotensin II-induced contractions in rabbit aorta in vitro.	kd	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	752258: Binding affinity to human angiotensin AT2 receptor by radioligand displacement assay	ic50	0.0001	uM
3-[butyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyridazine-4-carboxylic acid	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	0.0001	uM
Angiotensin Ii	1336308: Displacement of [125I]CGP 42112A from human recombinant AT2 receptor expressed in HEK293 cells measured after 4 hrs by scintillation counting method	ic50	0.0001	uM
2-ethyl-5,7-dimethyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-b]pyridine	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0001	uM
2-[2-butyl-4-oxo-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]-N,N-diethylacetamide	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0001	uM
(3R)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-phenylethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1285616: Displacement of [125I]CGP42112A from human recombinant AT2 receptor expressed in HEK293 cells	ic50	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-4-[(2S,3R)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-phenylethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]-2-[(4-hydroxyphenyl)methyl]-3-oxo-2,5-dihydro-1H-1,4-benzodiazepin-9-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	239147: Displacement of [125I]-Ang II from angiotensin II receptor type 2 in pig uterus myometrium	ki	0.0001	uM
(3S)-3-amino-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	751897: Binding affinity to human AT2 receptor by radioligand displacement assay	ki	0.0001	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]propanoic acid	31303: Inhibitory activity as antagonist of AII on guinea pig ileum	ic50	0.0001	uM
2-propyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-5,6,7,8-tetrahydrocyclohepta[d]imidazol-4-one	167381: Inhibition of angiotensin II-induced contractions in rabbit aorta in vitro.	kd	0.0001	uM
tert-butyl N-[2-[4-[[1-[2-bromo-5-(pentanoylamino)phenyl]-3-ethyl-5-oxo-1,2,4-triazol-4-yl]methyl]-3-fluorophenyl]phenyl]sulfonylcarbamate	38291: Inhibition of Angiotensin II receptor, type 2	ic50	0.0001	uM
2-ethyl-4-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methoxy]-5,6,7,8-tetrahydroquinoline	167381: Inhibition of angiotensin II-induced contractions in rabbit aorta in vitro.	kd	0.0001	uM
5-butyl-2-(2-phenylethyl)-4-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-1,2,4-triazol-3-one	166678: Antagonism of angiotensin-II mediated contraction of rabbit aortic rings expressed as pA2 (in vitro)	kd	0.0002	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid	254557: Binding affinity for angiotensin II receptor, type 2 in pig uterus myometrium using [125I]-Ang II as radioligand, in pH 7.4 Tris-HCl buffer for 1.5 hr at 25 degree C	ki	0.0002	uM
methyl 2-[2-butyl-4-oxo-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]acetate	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0002	uM
2-butyl-5-(2-oxo-2-pyrrolidin-1-ylethyl)-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-4-one	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0002	uM
4-[propyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyrimidine-5-carboxylic acid	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	0.0002	uM
3-[propyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyridazine-4-carboxylic acid	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	0.0002	uM
3-[butyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyrazine-2-carboxylic acid	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	0.0002	uM
6-fluoro-2-[propyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyridine-3-carboxylic acid	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	0.0002	uM
4-methyl-2-[propyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyridine-3-carboxylic acid	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	0.0002	uM
2-ethyl-5-(2-oxo-2-piperidin-1-ylethyl)-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-4-one	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0002	uM
(2R)-2-[[(2R)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-2-methyl-3-phenylpropanoic acid	167386: pA2 value was determined in the range of competitive inhibition in the in vitro rabbit aorta strip assay.	kd	0.0002	uM
(3S)-4-[[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1-[[(2S)-3-(4-hydroxyphenyl)-1-[[(2S,3S)-1-[[(2S)-3-(1H-imidazol-5-yl)-1-[[(2S)-3-(1H-imidazol-5-yl)-1-[[(2S,3S)-3-methyl-1-oxo-1-[[(2S)-3-oxo-1-phenylbutan-2-yl]amino]pentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopentan-2-yl]amino]-3-(methylamino)-4-oxobutanoic acid	39195: Binding affinity towards Angiotensin receptor from rabbit aorta	ic50	0.0002	uM
2-[2-butyl-4-oxo-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]-N,N-dimethylacetamide	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0002	uM
2-[2-ethyl-4-oxo-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]-N,N-dimethylacetamide	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0003	uM
2-methyl-4-[propyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyrimidine-5-carboxylic acid	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	0.0003	uM
N,N-diethyl-2-[2-ethyl-4-oxo-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]acetamide	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0003	uM
2-[2-butyl-4-oxo-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]-N-methyl-N-phenylacetamide	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0003	uM
5,7-dimethyl-2-propyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-b]pyridine	39195: Binding affinity towards Angiotensin receptor from rabbit aorta	ic50	0.0003	uM
4-[2-(N-(3,3-difluorocyclohexyl)anilino)-2-oxoethyl]-1-[(4-fluorophenyl)-methylcarbamoyl]piperidine-4-carboxylic acid	1993240: Displacement of ([125I]-Tyr4)-Angiotensin-II from recombinant human AT2R by gamma scintillation counter assay	ki	0.0003	uM
4-[2-(N-cyclohexylanilino)-2-oxoethyl]-1-[(3-fluorophenyl)-methylcarbamoyl]piperidine-4-carboxylic acid	1993240: Displacement of ([125I]-Tyr4)-Angiotensin-II from recombinant human AT2R by gamma scintillation counter assay	ki	0.0003	uM
4-[2-(N-(3,3-difluorocyclohexyl)-3-fluoroanilino)-2-oxoethyl]-1-[methyl(phenyl)carbamoyl]piperidine-4-carboxylic acid	1993240: Displacement of ([125I]-Tyr4)-Angiotensin-II from recombinant human AT2R by gamma scintillation counter assay	ki	0.0003	uM
4-[2-(N-(2-fluorophenyl)anilino)-2-oxoethyl]-1-[(4-fluorophenyl)-methylcarbamoyl]piperidine-4-carboxylic acid	1993240: Displacement of ([125I]-Tyr4)-Angiotensin-II from recombinant human AT2R by gamma scintillation counter assay	ki	0.0003	uM
4-[butyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]pyrimidine-5-carboxylic acid;hydrochloride	37542: Potency to antagonize the ability of angiotensin II to contract rabbit aorta	kd	0.0003	uM
Telmisartan	644751: Displacement of [125I]Sar1 Ile8-Ang 2 from angiotensin 2 AT2 receptor after 180 mins by gamma counting	ic50	0.0003	uM
2-[2-butyl-4-oxo-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazo[4,5-c]pyridin-5-yl]acetamide	39047: Inhibition of Angiotensin II induced contractions in rabbit aortic rings	ic50	0.0004	uM
methyl 5-[3-butyl-5-oxo-4-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-1,2,4-triazol-1-yl]pentanoate	166678: Antagonism of angiotensin-II mediated contraction of rabbit aortic rings expressed as pA2 (in vitro)	kd	0.0004	uM
4-[2-(N-cyclohexylanilino)-2-oxoethyl]-1-[(4-fluorophenyl)-methylcarbamoyl]piperidine-4-carboxylic acid	1993240: Displacement of ([125I]-Tyr4)-Angiotensin-II from recombinant human AT2R by gamma scintillation counter assay	ki	0.0004	uM
1-[(4-fluorophenyl)-methylcarbamoyl]-4-[2-oxo-2-(N-phenylanilino)ethyl]piperidine-4-carboxylic acid	1993240: Displacement of ([125I]-Tyr4)-Angiotensin-II from recombinant human AT2R by gamma scintillation counter assay	ki	0.0004	uM
(2S,3S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[2-(methylamino)acetyl]amino]pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoic acid	31303: Inhibitory activity as antagonist of AII on guinea pig ileum	ic50	0.0004	uM
butyl N-[3-[4-(imidazol-1-ylmethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate	1169023: Binding affinity to AT2 receptor (unknown origin)	ki	0.0004	uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
PD 123319	increases expression, affects binding, decreases activity, decreases reaction	2
tetrathiomolybdate	decreases expression	1
candesartan	affects binding, decreases activity, decreases reaction, increases expression	1
entinostat	decreases expression	1
Menthol	decreases expression	1
Paraquat	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases methylation	1
Copper Sulfate	affects expression	1

ChEMBL screening assays

244 unique, capped per target: 188 binding, 56 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4327279	Binding	Antagonist activity at angiotensin-2 receptor (unknown origin)	Naphthalene, a versatile platform in medicinal chemistry: Sky-high perspective. — Eur J Med Chem
CHEMBL642870	Functional	The compound was tested for its inhibitory activity as antagonist of AII on guinea pig ileum	Synthesis and biological activity of angiotensin II analogues containing a Val-His replacement, Val psi[CH(CONH2)NH]His. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1V6	Abcam A-549 AGTR2 KO	Cancer cell line	Male
CVCL_E5JT	CHO-K1/AT2/Gqi5	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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