AVPR2

Summary

AVPR2 (arginine vasopressin receptor 2, HGNC:897) is a protein-coding gene on chromosome Xq28, encoding Vasopressin V2 receptor (P30518). G-protein-coupled receptor for arginine vasopressin, an antidiuretic that promotes renal water reabsorption. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes the vasopressin receptor, type 2, also known as the V2 receptor, which belongs to the seven-transmembrane-domain G protein-coupled receptor (GPCR) superfamily, and couples to Gs thus stimulating adenylate cyclase. The subfamily that includes the V2 receptor, the V1a and V1b vasopressin receptors, the oxytocin receptor, and isotocin and mesotocin receptors in non-mammals, is well conserved, though several members signal via other G proteins. All bind similar cyclic nonapeptide hormones. The V2 receptor is expressed in the kidney tubule, predominantly in the distal convoluted tubule and collecting ducts, where its primary property is to respond to the pituitary hormone arginine vasopressin (AVP) by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of this gene is lost, the disease Nephrogenic Diabetes Insipidus (NDI) results. The V2 receptor is also expressed outside the kidney although its tissue localization is uncertain. When these ’extrarenal receptors’ are stimulated by infusion of a V2 selective agonist (dDAVP), a variety of clotting factors are released into the bloodstream. The physiologic importance of this property is not known - its absence does not appear to be detrimental in NDI patients. The gene expression has also been described in fetal lung tissue and lung cancer associated with alternative splicing.

Source: NCBI Gene 554 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diabetes insipidus, nephrogenic, X-linked (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 434 total — 66 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes — 51 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000054

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:897
Approved symbol	AVPR2
Name	arginine vasopressin receptor 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	V2R
Ensembl gene	ENSG00000126895
Ensembl biotype	protein_coding
OMIM	300538
Entrez	554

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000337474, ENST00000370049, ENST00000430697, ENST00000434679, ENST00000646375, ENST00000881289, ENST00000881290, ENST00000881291, ENST00000960389

RefSeq mRNA: 2 — MANE Select: NM_000054 NM_000054, NM_001146151

CCDS: CCDS14735, CCDS55539

Canonical transcript exons

ENST00000646375 — 4 exons

Exon	Start	End
ENSE00001276810	153905532	153906416
ENSE00001419977	153906523	153907166
ENSE00002231876	153904974	153905170
ENSE00003822128	153904673	153904771

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 86.31.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	86.31	gold quality
type B pancreatic cell	CL:0000169	83.60	gold quality
olfactory bulb	UBERON:0002264	82.82	gold quality
omental fat pad	UBERON:0010414	76.75	gold quality
peritoneum	UBERON:0002358	76.72	gold quality
adipose tissue of abdominal region	UBERON:0007808	76.12	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.94	gold quality
heart left ventricle	UBERON:0002084	74.32	gold quality
cardiac ventricle	UBERON:0002082	73.97	gold quality
adipose tissue	UBERON:0001013	73.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.10	gold quality
buccal mucosa cell	CL:0002336	72.98	gold quality
metanephros cortex	UBERON:0010533	72.64	gold quality
granulocyte	CL:0000094	72.63	gold quality
vena cava	UBERON:0004087	72.44	silver quality
connective tissue	UBERON:0002384	72.37	gold quality
male germ cell	CL:0000015	71.57	gold quality
triceps brachii	UBERON:0001509	71.45	gold quality
tendon of biceps brachii	UBERON:0008188	71.12	silver quality
gluteal muscle	UBERON:0002000	71.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.71	gold quality
lower esophagus	UBERON:0013473	70.58	gold quality
parotid gland	UBERON:0001831	70.28	gold quality
sperm	CL:0000019	70.25	gold quality
heart	UBERON:0000948	69.97	gold quality
adult mammalian kidney	UBERON:0000082	69.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.44	gold quality
vastus lateralis	UBERON:0001379	69.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	69.12	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ASCL1, BARHL2, INPP5K, NRF1, TFAM

miRNA regulators (miRDB)

22 targeting AVPR2, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-3162-5P	95.67	67.53	794
HSA-MIR-25-5P	87.02	64.95	84

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• proteolytic cleavage of the V2 receptor requires a defined conformation and might play a role in signal termination at elevated hormone concentrations (PMID:10561596)
• A novel type of contiguous gene deletion of AVPR2 has been identified in unrelated Japanese kindreds with nephrogenic diabetes insipidus. (PMID:11754100)
• A new mutation associated with nephrogenic diabetes insipidus was isolated: a 6-AA deletion between G107 and C112. (PMID:11868598)
• Mutations causing NDI include R106C, F287L, and R337X. (PMID:11916004)
• a single amino acid difference in the first extracellular loop determines the efficiency of cell surface expression (PMID:11923476)
• HV2R has a serine/threonine motif that is required for retention in the cytoplasm (PMID:12482593)
• palmitoylation enhances the recruitment of beta-arrestin to the activated V2 vasopressin receptor thus facilitating processes requiring the scaffolding action of beta-arrestin (PMID:12900404)
• V2 vasopressin receptor degradation is regulated by agonist-promoted ubiquitination (PMID:12960162)
• examination of interaction with beta-arrestin and trafficking patterns by heterodimerization with V1 vasopressin receptor (PMID:14757828)
• analysis of pharmacochaperone cell surface delivery with a three-dimensional homology model of the antagonist-bound hV2R (PMID:15319430)
• a C-terminal region of the V2R important for calmodulin interaction is also important in modulation of V2R elevation of intracellular Ca2 (PMID:15319442)
• V2 vasopressin receptor has a role in inhibiting signaling through its interaction with receptor dimer and G protein (PMID:15452133)
• The data suggested that lysine 231 and glutamate 268 might interact with each other and might play a role in promoting GDP/GTP exchange in V2 vasopressin receptors. (PMID:16115624)
• Results show that the hydrophobic amino acid residues in the membrane-proximal C tail of the G protein-coupled vasopressin V2 receptor are necessary for transport-competent receptor folding. (PMID:16162341)
• Genetic analysis confirmed a mutation in AVPR2. (PMID:16240160)
• V2R-V206D and V2R-S167T were rescued and matured to a greater extent, suggesting that the rescuing activity of a pharmacological versus chemical chaperone is broader and stronger (PMID:16267275)
• molecular dynamics analysis of mechanism of desmopressin binding in vasopressin V2 receptor versus vasopressin V1a and oxytocin receptors (PMID:16333859)
• After VP stimulation of renal epithelial cells, AQP2 accumulates at the cell surface, while the V2R is actively internalized. This endocytotic block may involve a reduced capacity of phosphorylated AQP2 to interact with the endocytotic machinery. (PMID:16563128)
• Most missense AVPR2 mutations lead to receptors that are trapped intracellularly; a few mutant receptors reach the cell surface but are unable to bind AVP or to properly trigger an intracellular cyclic adenosine monophosphate signal. (PMID:16580609)
• The disorder nephrogenic diabetes insipidus (NDI) is inherited in an X-linked or autosomal fashion due to mutations in the genes encoding V2R or AQP2, respectively. (PMID:16825342)
• Two novel mutations were identified in each of AVPR2 and AQP2 underlying Congenital Nephrogenic Diabetes Insipidus in Arab families. (PMID:16845277)
• Findings of mutations scattered over the entire coding region of the AVPR2 gene are a valuable model to determine structure function relationship in G-protein-coupled receptor-related diseases. (PMID:17020465)
• These findings suggest that the two patients in a Chinese family suffering from congenital nephrogenic diabetes insipidus had a 5,995-bp deletion and 3-bp (GAG) insertion at Xq28. The deletion contained the entire AVPR2 gene and exon 22 of the C1 gene. (PMID:17101063)
• Y205F missense mutation would cause nephrogenic diabetes insipidus. (PMID:17216256)
• Mutations involved in nephrogenic syndrome of inappropriate antidiuresis in men and womwen. (PMID:17229917)
• Primary nocturanl enuresis and coexisting nephrogenic diabetes insipidus, as a result of a novel nonsense mutation in the V2R gene (C358X). (PMID:17389737)
• Urinary AQP2 excretion was absent in patients with severely debilitating mutations, a novel total deletion of the A VPR2 gene, and a novel nonsense mutation W296X. (PMID:17550212)
• V(2)R mRNA was expressed in medullary TAL (MTAL), macula densa, connecting tubule, and cortical and medullary collecting duct, and was weakly expressed in cortical TAL and distal convoluted tubule in rat, mouse, and human. (PMID:17626156)
• A novel missense mutation in exon 3 of the AVPR2 gene was identified in the nephrogenic diabetes insipidus patients. (PMID:17941907)
• Ubiquitin-like protein PLIC-2 is identified as a negative regulator of G protein-coupled receptor endocytosis. (PMID:18199683)
• The protective mechanism exerted by OPC-31260 stems from its influence on the renal vasopressin V(2) receptors. These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans. (PMID:18288441)
• Clinical nephrogenic diabetes insipidus phenotypes may correlate with the X-inactivation patterns in female carriers with heterozygote vasopressin type 2 receptor gene mutations. (PMID:18323675)
• Data demonstrated a direct and specific interaction between vasopressin V2 receptor and GC1q-Rthese two proteins via the arginine cluster of vasopressin V2 receptor. (PMID:18358546)
• identified a novel phosphorylation site (Ser(255))in the third intracellular loop that could be phosphorylated in vitro by protein kinase A, but not by Akt kinase (PMID:18578504)
• AVPR2 variants & mutations in nephrogenic diabetes insipidus(NDI); spectrum of mutations varies from rare gene variants or polymorphisms not causing NDI to rare mutations causing NDI, among which arginine and tyrosine are the most common missense (PMID:18726898)
• adults with intermittent, severe hyponatraemia may have a constitutively activating mutation in the AVPR2 with resultant nephrogenic syndrome of inappropriate antidiuresis (PMID:18753429)
• both pAVP (1.6-fold versus controls; P = 0.048) and inner ear V2R mRNA expression (41.5-fold versus controls; P = 0.022) were significantly higher in Meniere’s patients than controls (PMID:19094077)
• Wild-type V2R localized to the cell membrane while L57R V2R remained intracellular. (PMID:19170711)
• Data indicate that the vasopressin 2 receptor-R137C and V2R-R137L mutants traffic considerably more efficiently to the plasma membrane than V2R-R137H, identifying this as a potentially important mutation-dependent difference affecting V2R function. (PMID:19179480)
• Our study shows for the first time that renal cancer may effectively synthesize and express the V2-R. (PMID:19217806)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	avpr2aa	ENSDARG00000007436
danio_rerio	avpr2ab	ENSDARG00000029219
mus_musculus	Avpr2	ENSMUSG00000031390
rattus_norvegicus	Avpr2	ENSRNOG00000059862
drosophila_melanogaster	CCAP-R	FBGN0039396

Paralogs (16): NPFFR2 (ENSG00000056291), GNRHR (ENSG00000109163), CCKBR (ENSG00000110148), HCRTR1 (ENSG00000121764), GALR3 (ENSG00000128310), HCRTR2 (ENSG00000137252), NPFFR1 (ENSG00000148734), CCKAR (ENSG00000163394), AVPR1A (ENSG00000166148), GALR1 (ENSG00000166573), GPR22 (ENSG00000172209), GPR150 (ENSG00000178015), OXTR (ENSG00000180914), FFAR4 (ENSG00000186188), QRFPR (ENSG00000186867), AVPR1B (ENSG00000198049)

Protein

Protein identifiers

Vasopressin V2 receptor — P30518 (reviewed: P30518)

Alternative names: AVPR V2, Antidiuretic hormone receptor, Renal-type arginine vasopressin receptor

All UniProt accessions (3): P30518, C9JV81, F8WET1

UniProt curated annotations — full annotation on UniProt →

Function. G-protein-coupled receptor for arginine vasopressin, an antidiuretic that promotes renal water reabsorption. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (cAMP). AVPR2 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity.

Subunit / interactions. Interacts with ARRDC4. Identified in a complex containing at least ARRDC4, V2R and HGS. Interacts with TMEM147. Interacts (when phosphorylated) with ARRB2; the interaction is associated with internalization of the receptor and short-term desensitization to the ligand.

Subcellular location. Cell membrane.

Tissue specificity. Kidney.

Post-translational modifications. Phosphorylation of the P-X-P-P motif promotes association with beta-arrestin ARRB2, leading to receptor desensitization and negative regulation of G-protein coupled receptor signaling.

Disease relevance. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) [MIM:300539] Characterized by an inability to excrete a free water load, with inappropriately concentrated urine and resultant hyponatremia, hypoosmolarity, and natriuresis. The disease is caused by variants affecting the gene represented in this entry. Diabetes insipidus, nephrogenic, 1, X-linked (NDI1) [MIM:304800] A disorder caused by the inability of the renal collecting ducts to absorb water in response to arginine vasopressin. Characterized by excessive water drinking (polydipsia), excessive urine excretion (polyuria), persistent hypotonic urine, and hypokalemia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The P-X-P-P motif is phosphorylated in response to ligand binding, promoting. association with beta-arrestin ARRB2.

Similarity. Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P30518-1	1	yes
P30518-2	2

RefSeq proteins (2): NP_000045, NP_001139623 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000161	Vprsn_rcpt_V2	Family
IPR000276	GPCR_Rhodpsn	Family
IPR001817	Vasoprsn_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (173 total): sequence variant 99, mutagenesis site 13, helix 13, modified residue 11, topological domain 8, transmembrane region 7, strand 6, turn 3, region of interest 3, compositionally biased region 2, lipid moiety-binding region 2, splice variant 2, chain 1, short sequence motif 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7DFC	X-RAY DIFFRACTION	2.49
9HAP	ELECTRON MICROSCOPY	2.5
9HB3	ELECTRON MICROSCOPY	2.5
7DFA	X-RAY DIFFRACTION	2.54
4JQI	X-RAY DIFFRACTION	2.6
7DW9	ELECTRON MICROSCOPY	2.6
7KH0	ELECTRON MICROSCOPY	2.8
9WSV	ELECTRON MICROSCOPY	2.8
9WSW	ELECTRON MICROSCOPY	2.8
9WSX	ELECTRON MICROSCOPY	2.8
9UVW	ELECTRON MICROSCOPY	2.89
9UYN	ELECTRON MICROSCOPY	2.9
9U80	ELECTRON MICROSCOPY	2.94
9UVY	ELECTRON MICROSCOPY	2.98
9LZ2	ELECTRON MICROSCOPY	3
9UVV	ELECTRON MICROSCOPY	3.02
9U81	ELECTRON MICROSCOPY	3.08
9LY2	ELECTRON MICROSCOPY	3.1
7DF9	X-RAY DIFFRACTION	3.17
8WU1	ELECTRON MICROSCOPY	3.2
9UYI	ELECTRON MICROSCOPY	3.2
7DFB	X-RAY DIFFRACTION	3.28
8JRV	ELECTRON MICROSCOPY	3.3
9UYH	ELECTRON MICROSCOPY	3.3
9UYJ	ELECTRON MICROSCOPY	3.3
9UYL	ELECTRON MICROSCOPY	3.3
9UVX	ELECTRON MICROSCOPY	3.31
9BT8	ELECTRON MICROSCOPY	3.34
9CX9	ELECTRON MICROSCOPY	3.34
9LY3	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30518-F1	76.84	0.32

Antibody-complex structures (SAbDab): 29 — 4JQI, 6NI2, 6U1N, 7BB6, 7BB7, 7DF9, 7DFA, 7DFB, 7DFC, 7DW9, 7KH0, 7R0C, 7R0J, 8GOC, 8I10, 8WRZ, 8WU1, 9BT8, 9CX3, 9CX9, 9HB3, 9UYH, 9UYI, 9UYJ, 9UYL (+4 more)

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 (13): 347, 350, 357, 359, 360, 362, 363, 364, 369, 370, 371, 341, 342

Disulfide bonds (1): 112–192

Glycosylation sites (1): 22

Mutagenesis-validated functional residues (13):

Position	Phenotype
31	does not affect signaling and ability to activate adenylate cyclase.
96	strongly decreased signaling and ability to activate adenylate cyclase.
105	strongly decreased signaling and ability to activate adenylate cyclase.
123	does not affect arginine vasopressin-binding.
174	strongly decreased signaling and ability to activate adenylate cyclase.
202	does not affect signaling and ability to activate adenylate cyclase.
205	strongly decreased signaling and ability to activate adenylate cyclase.
287	strongly decreased signaling and ability to activate adenylate cyclase.
291	does not affect arginine vasopressin-binding.
302	does not affect signaling and ability to activate adenylate cyclase.
312	does not affect arginine vasopressin-binding.
341	reduced palmitoylation, reduced cell surface localization but coupling to g protein unaffected.
342	reduced palmitoylation, reduced cell surface localization but coupling to g protein unaffected.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-388479	Vasopressin-like receptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9036092	Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI)

MSigDB gene sets: 223 (showing top): GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, REACTOME_MEMBRANE_TRAFFICKING, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_WATER_TRANSPORT, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_ADENYLATE_CYCLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_VASOCONSTRICTION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION

GO Biological Process (20): regulation of systemic arterial blood pressure by vasopressin (GO:0001992), positive regulation of systemic arterial blood pressure (GO:0003084), renal water retention (GO:0003092), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), activation of adenylate cyclase activity (GO:0007190), hemostasis (GO:0007599), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), telencephalon development (GO:0021537), cellular response to hormone stimulus (GO:0032870), response to cytokine (GO:0034097), positive regulation of vasoconstriction (GO:0045907), renal water absorption (GO:0070295), positive regulation of intracellular signal transduction (GO:1902533), signal transduction (GO:0007165), negative regulation of urine volume (GO:0035811), positive regulation of blood pressure (GO:0045777)

GO Molecular Function (4): vasopressin receptor activity (GO:0005000), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), signaling receptor activity (GO:0038023)

GO Cellular Component (8): endosome (GO:0005768), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), endocytic vesicle (GO:0030139), clathrin-coated endocytic vesicle membrane (GO:0030669), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Aquaporin-mediated transport	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
SLC transporter disorders	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
cytoplasm	3
G protein-coupled receptor signaling pathway	2
cell population proliferation	2
regulation of cell population proliferation	2
cytoplasmic vesicle	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
regulation of systemic arterial blood pressure by hormone	1
regulation of systemic arterial blood pressure	1
positive regulation of blood pressure	1
negative regulation of urine volume	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
positive regulation of adenylate cyclase activity	1
regulation of body fluid levels	1
positive regulation of cellular process	1
negative regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
forebrain development	1
anatomical structure development	1
response to hormone	1
cellular response to chemical stimulus	1
cellular response to endogenous stimulus	1
response to peptide	1
regulation of vasoconstriction	1
vasoconstriction	1
positive regulation of multicellular organismal process	1
renal water transport	1
renal absorption	1
positive regulation of signal transduction	1
intracellular signal transduction	1
regulation of intracellular signal transduction	1
cell communication	1
cellular process	1

Protein interactions and networks

STRING

1590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AVPR2	AVP	P01185	988
AVPR2	ARRB1	P49407	982
AVPR2	AQP2	P41181	981
AVPR2	ARRB2	P32121	889
AVPR2	ARHGAP4	P98171	866
AVPR2	GNAO1	P09471	838
AVPR2	RENBP	P51606	824
AVPR2	C1QTNF1	Q9BXJ1	766
AVPR2	OXT	P01178	758
AVPR2	NAA10	P41227	748
AVPR2	L1CAM	P32004	745
AVPR2	SLC12A1	Q13621	722
AVPR2	REN	P00797	709
AVPR2	VN1R1	Q9GZP7	690
AVPR2	OLIG3	Q7RTU3	668

IntAct

17 interactions, top by confidence:

A	B	Type	Score
AVPR2	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
	AVPR2	psi-mi:“MI:0915”(physical association)	0.560
COMT	AVPR2	psi-mi:“MI:0915”(physical association)	0.560
ARRDC4	AVPR2	psi-mi:“MI:0915”(physical association)	0.400
AVPR2	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
AVPR2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
AVPR2	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
AVPR2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
AVPR2	ATP9B	psi-mi:“MI:0914”(association)	0.350
	AVPR2	psi-mi:“MI:0915”(physical association)	0.000
COMT	AVPR2	psi-mi:“MI:0915”(physical association)	0.000
SLC41A1	AVPR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (127): ARRDC4 (Affinity Capture-Western), HGS (Affinity Capture-Western), CLTC (Affinity Capture-Western), AVPR2 (Affinity Capture-Western), AVPR2 (Affinity Capture-Western), AVPR2 (Reconstituted Complex), AVP (Reconstituted Complex), AVPR2 (Two-hybrid), SLC41A1 (Two-hybrid), FXYD6-FXYD2 (Two-hybrid), MAPK3 (Affinity Capture-Western), ARRB2 (Affinity Capture-Western), C1QTNF1 (Two-hybrid), C1QTNF1 (Reconstituted Complex), AVPR2 (Affinity Capture-Western)

ESM2 similar proteins: A6NGC4, A6NKX4, A6NM10, D3YZZ2, O35595, O46547, O60391, O77808, O95528, P30518, P43119, P46092, P46095, P48044, P48748, Q14626, Q3SYU3, Q3ZAV1, Q4U2R8, Q4W8A3, Q5RF19, Q5U419, Q64385, Q684M3, Q6UXD7, Q6UXT9, Q6YNI2, Q863Y8, Q86SM5, Q8CFZ5, Q8IXF9, Q8WUG5, Q91X56, Q924U0, Q96S37, Q99MF4, Q9BGL8, Q9BZ11, Q9H1Z9, Q9H228

Diamond homologs: A0A2L0VBG2, O18821, O42329, O77808, O88721, P30518, P30560, P30968, P30969, P32236, P32237, P32307, P37288, P48044, P49922, P70536, P97266, Q00788, Q01776, Q18775, Q19PY9, Q24563, Q25188, Q2V2K5, Q5QD12, Q5QD21, Q63384, Q8CH60, Q8IS44, Q8SPZ1, Q90252, Q90334, Q923X8, Q923Y2, Q93126, Q95JG1, Q95MG6, Q95MH6, Q96P88, Q9BZJ6

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
AVP	up-regulates	AVPR2	binding
AVPR2	“up-regulates activity”	GNAS	binding
AVPR2	“up-regulates activity”	GNAL	binding
vasopressin	“up-regulates activity”	AVPR2	“chemical activation”
conivaptan	“down-regulates activity”	AVPR2	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	66
Likely pathogenic	37
Uncertain significance	97
Likely benign	129
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
10835	NM_000054.7(AVPR2):c.738del (p.Arg247fs)	Pathogenic
10836	NM_000054.7(AVPR2):c.395C>A (p.Ala132Asp)	Pathogenic
10837	NM_000054.7(AVPR2):c.553G>T (p.Gly185Cys)	Pathogenic
10840	NM_000054.7(AVPR2):c.337C>T (p.Arg113Trp)	Pathogenic
10841	NM_000054.7(AVPR2):c.682_683insC (p.Ile228fs)	Pathogenic
10842	NM_000054.7(AVPR2):c.213G>A (p.Trp71Ter)	Pathogenic
10843	NM_000054.7(AVPR2):c.839A>G (p.Tyr280Cys)	Pathogenic
10844	NM_000054.7(AVPR2):c.1009C>T (p.Arg337Ter)	Pathogenic
10845	NM_000054.7(AVPR2):c.253G>A (p.Asp85Asn)	Pathogenic
10846	NM_000054.7(AVPR2):c.602G>A (p.Gly201Asp)	Pathogenic
10847	NM_000054.7(AVPR2):c.738dup (p.Arg247fs)	Pathogenic
10848	NM_000054.7(AVPR2):c.102del (p.Leu35fs)	Pathogenic
10849	NM_000054.7(AVPR2):c.410G>A (p.Arg137His)	Pathogenic
10850	NM_000054.7(AVPR2):c.541C>T (p.Arg181Cys)	Pathogenic
10851	NM_000054.7(AVPR2):c.313T>G (p.Phe105Val)	Pathogenic
10852	NM_000054.7(AVPR2):c.137T>A (p.Ile46Lys)	Pathogenic
10854	NM_000054.7(AVPR2):c.409C>T (p.Arg137Cys)	Pathogenic
10855	NM_000054.7(AVPR2):c.410G>T (p.Arg137Leu)	Pathogenic
1299878	NM_000054.7(AVPR2):c.910+1G>A	Pathogenic
1324012	NM_000054.7(AVPR2):c.871C>T (p.Gln291Ter)	Pathogenic
1994770	NM_000054.7(AVPR2):c.911-1G>A	Pathogenic
204318	NM_000054.7(AVPR2):c.388A>T (p.Ile130Phe)	Pathogenic
2138781	NM_000054.7(AVPR2):c.935T>A (p.Leu312Ter)	Pathogenic
2152356	NM_000054.7(AVPR2):c.238C>T (p.His80Tyr)	Pathogenic
235612	NM_000054.7(AVPR2):c.392T>C (p.Leu131Pro)	Pathogenic
2422254	NC_000023.10:g.(?153166735)(153170999_?)del	Pathogenic
2435099	NM_000054.7(AVPR2):c.348_349delinsAGG (p.Tyr117fs)	Pathogenic
2504686	NM_000054.7(AVPR2):c.296G>A (p.Trp99Ter)	Pathogenic
2572644	NM_000054.7(AVPR2):c.468G>A (p.Trp156Ter)	Pathogenic
2577986	NM_000054.7(AVPR2):c.262G>A (p.Val88Met)	Pathogenic

SpliceAI

341 predictions. Top by Δscore:

Variant	Effect	Δscore
X:153905530:A:AG	acceptor_gain	1.0000
X:153905530:A:T	acceptor_loss	1.0000
X:153905530:AGCT:A	acceptor_gain	1.0000
X:153905531:G:GA	acceptor_gain	1.0000
X:153905531:GC:G	acceptor_gain	1.0000
X:153905531:GCT:G	acceptor_gain	1.0000
X:153905531:GCTG:G	acceptor_gain	1.0000
X:153905531:GCTGT:G	acceptor_gain	1.0000
X:153904769:CAGGT:C	donor_loss	0.9900
X:153904772:G:GC	donor_loss	0.9900
X:153904773:T:A	donor_loss	0.9900
X:153904970:CCAG:C	acceptor_loss	0.9900
X:153904973:G:GT	acceptor_loss	0.9900
X:153905518:C:CA	acceptor_gain	0.9900
X:153905533:T:A	acceptor_gain	0.9900
X:153905958:G:GT	donor_gain	0.9900
X:153904767:GCCAG:G	donor_gain	0.9800
X:153904972:A:AG	acceptor_gain	0.9800
X:153904973:G:GG	acceptor_gain	0.9800
X:153904973:GGA:G	acceptor_gain	0.9800
X:153905171:G:GG	donor_gain	0.9800
X:153904967:T:TA	acceptor_gain	0.9700
X:153904972:AG:A	acceptor_gain	0.9700
X:153904973:GG:G	acceptor_gain	0.9700
X:153904973:GGACT:G	acceptor_gain	0.9700
X:153905167:TCCGG:T	donor_loss	0.9700
X:153905169:CGG:C	donor_loss	0.9700
X:153905170:GGTAA:G	donor_loss	0.9700
X:153905171:G:GA	donor_loss	0.9700
X:153904772:G:GG	donor_gain	0.9600

AlphaMissense

2360 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:153906038:T:C	F178L	0.997
X:153906040:C:A	F178L	0.997
X:153906040:C:G	F178L	0.997
X:153906093:T:G	F196C	0.997
X:153905820:T:G	F105C	0.996
X:153905819:T:C	F105L	0.995
X:153905821:C:A	F105L	0.995
X:153905821:C:G	F105L	0.995
X:153906017:A:C	S171R	0.994
X:153906019:C:A	S171R	0.994
X:153906019:C:G	S171R	0.994
X:153905840:T:A	C112S	0.993
X:153905841:G:C	C112S	0.993
X:153906579:T:A	W323R	0.993
X:153906579:T:C	W323R	0.993
X:153906365:T:C	F287L	0.992
X:153906367:C:A	F287L	0.992
X:153906367:C:G	F287L	0.992
X:153906039:T:G	F178C	0.991
X:153906156:C:A	P217H	0.991
X:153905820:T:C	F105S	0.990
X:153906555:A:C	S315R	0.990
X:153906557:C:A	S315R	0.990
X:153906557:C:G	S315R	0.990
X:153906092:T:C	F196L	0.989
X:153906094:T:A	F196L	0.989
X:153906094:T:G	F196L	0.989
X:153906564:A:C	S318R	0.989
X:153906566:C:A	S318R	0.989
X:153906566:C:G	S318R	0.989

dbSNP variants (sampled 300 via entrez): RS1000100704 (X:153902425 C>G), RS1001509041 (X:153903739 G>A,T), RS1001942827 (X:153907230 G>A), RS1002078817 (X:153906879 C>T), RS1002191040 (X:153900697 C>T), RS1002605460 (X:153904239 G>A), RS1002741120 (X:153903995 T>C), RS1006013560 (X:153904316 C>T), RS1006684675 (X:153901653 C>T), RS1006703232 (X:153901299 C>T), RS1007734235 (X:153903095 G>A), RS1008116729 (X:153902832 T>C), RS1008602008 (X:153906560 C>G), RS1009194381 (X:153906851 C>A,T), RS1009994980 (X:153901954 G>C)

Disease associations

OMIM: gene MIM:300538 | disease phenotypes: MIM:304800, MIM:300539, MIM:300673

GenCC curated gene-disease

Disease	Classification	Inheritance
diabetes insipidus, nephrogenic, X-linked	Definitive	X-linked
nephrogenic syndrome of inappropriate antidiuresis	Strong	X-linked
nephrogenic diabetes insipidus	Supportive	Autosomal dominant

Mondo (4): diabetes insipidus, nephrogenic, X-linked (MONDO:0010581), nephrogenic diabetes insipidus (MONDO:0016383), nephrogenic syndrome of inappropriate antidiuresis (MONDO:0010356), severe neonatal-onset encephalopathy with microcephaly (MONDO:0010397)

Orphanet (3): Arginine vasopressin resistance (Orphanet:223), Nephrogenic syndrome of inappropriate antidiuresis (Orphanet:93606), MECP2-related severe neonatal encephalopathy (Orphanet:209370)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000009	Functional abnormality of the bladder
HP:0000021	Megacystis
HP:0000072	Hydroureter
HP:0000083	Renal insufficiency
HP:0000103	Polyuria
HP:0000737	Irritability
HP:0000873	Diabetes insipidus
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001561	Polyhydramnios
HP:0001945	Fever
HP:0001955	Unexplained fevers
HP:0001959	Polydipsia
HP:0001986	Hypertonic dehydration
HP:0002013	Vomiting
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002039	Anorexia
HP:0002197	Generalized-onset seizure
HP:0002902	Hyponatremia
HP:0003158	Hyposthenuria
HP:0003228	Hypernatremia
HP:0003351	Decreased circulating renin concentration
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018500	Diabetes Insipidus, Nephrogenic	C12.050.351.968.419.135.500; C12.200.777.419.135.500; C12.950.419.135.500
C566878	Encephalopathy, Neonatal Severe, Due To Mecp2 Mutations (supp.)
C564491	Nephrogenic Syndrome of Inappropriate Antidiuresis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1790 (SINGLE PROTEIN), CHEMBL2363078 (PROTEIN FAMILY), CHEMBL4523980 (SELECTIVITY GROUP), CHEMBL5482972 (CHIMERIC PROTEIN)

Molecules with ChEMBL bioactivity

51 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 234,009 (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
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1201	THIOTHIXENE	4	13,101
CHEMBL1201284	CINACALCET	4	5,917
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1201346	BALSALAZIDE	4	8,319
CHEMBL126224	IPRINDOLE	4	4,398
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL1429	DESMOPRESSIN	4	122
CHEMBL1617	RIFAXIMIN	4	13,380
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL1755	CONIVAPTAN	4	3,108
CHEMBL180022	NERATINIB	4	9,404
CHEMBL252556	IDEBENONE	4	8,581
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL328190	LASOFOXIFENE	4	10,617
CHEMBL3301668	CARBETOCIN	4	1,721
CHEMBL344159	TOLVAPTAN	4	3,645
CHEMBL373742	VASOPRESSIN	4
CHEMBL374478	RIFAMPIN	4
CHEMBL382301	ATOSIBAN	4
CHEMBL395429	OXYTOCIN	4
CHEMBL416956	MEFLOQUINE	4
CHEMBL420762	MOZAVAPTAN	4
CHEMBL422	TRIFLUOPERAZINE	4
CHEMBL434394	NEBIVOLOL	4
CHEMBL46516	FLUSPIRILENE	4
CHEMBL535	SUNITINIB	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Vasopressin and oxytocin receptors

Most potent curated ligand interactions (63 total), top 25:

Ligand	Action	Affinity	Parameter
[125I]d(CH2)5[D-Ile2,Ile4,Tyr-NH29]AVP	Antagonist	9.5	pKd
conivaptan	Antagonist	9.44	pKi
[3H]AVP (human, mouse, rat)	Full agonist	9.4	pKd
tolvaptan	Antagonist	9.37	pKi
satavaptan	Antagonist	9.3	pKi
[3H]SR 121463A	Inverse agonist	9.3	pKd
[125I]d(CH2)5[D-Ile2,Val4,Tyr-NH29]AVP	Antagonist	9.2	pKd
lixivaptan	Inverse agonist	9.2	pKi
vasopressin	Full agonist	9.1	pKi
[3H]dDAVP	Full agonist	9.1	pKd
dVDAVP	Full agonist	9.1	pKi
d(CH2)5[D-Tyr(Et)2,Val4,Tyr-NH29]AVP	Antagonist	9.1	pKi
[125I]d(CH2)5[D-Tyr(Et)2,Ile4,Tyr-NH29]AVP	Antagonist	9.1	pKd
[125I]d(CH2)5[D-Tyr(Et)2,Val4,Tyr-NH29]AVP	Antagonist	9.1	pKd
RWJ-351647	Antagonist	9.0	pKi
YM 471	Antagonist	8.9	pKi
SKF-105494	Antagonist	8.9	pKi
[3H]desGly-NH2[D-Ile2,Ile4]VP		8.6	pKd
desmopressin	Full agonist	8.6	pKi
LVP	Full agonist	8.5	pKi
[Val4]AVP	Full agonist	8.4	pKi
d(CH2)5[D-Ile2,Ile4]AVP	Antagonist	8.4	pKi
dAVP	Full agonist	8.3	pKi
d(CH2)5[Tyr(Et)2,Val4,des-Gly9]AVP	Antagonist	8.3	pKi
arginine vasotocin	Full agonist	8.2	pKi

Binding affinities (BindingDB)

160 measured of 184 human assays (186 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
CAS_50-56-6	KI	0.5 nM
[3-[[2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetyl]amino]-2-[2-(trifluoromethyl)phenyl]propyl] carbamate	IC50	1 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
5H-1-benzazepin-5-ylidene acetamide, 10j	EC50	1.25 nM
5H-1-benzazepin-5-ylidene acetamide, 10i	EC50	3.13 nM
tert-butyl N-[2-[[2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetyl]amino]-1-[2-(trifluoromethyl)phenyl]ethyl]carbamate	IC50	4 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]-N-[(2R)-1-hydroxy-3-[3-(trifluoromethyl)phenyl]propan-2-yl]acetamide	IC50	4 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
5-(4-chlorophenyl)-2-[[3-[(2,6-dichlorophenyl)methyl]-1H-1,2,4-triazol-5-yl]methyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-one	IC50	4 nM	US-9187466: Bisaryl-bonded aryltriazolones and use thereof
3-chloro-4-[16-methyl-(12S)-2,10-diazatetracyclo[11.2.1.02,12.04,9]hexadeca-4(9),5,7-trien-10-ylcarbonyl]-1-(2-phenylphenylcarboxamido)benzene	IC50	4 nM
3-chloro-4-[16-ethyl-2,10-diazatetracyclo[11.2.1.02,12.04,9]hexadeca-4(9),5,7-trien-10-ylcarbonyl]-1-(2-phenylphenylcarboxamido)benzene	IC50	4 nM
5-(4-chlorophenyl)-2-[[3-[(2,6-dichlorophenyl)methyl]-1H-1,2,4-triazol-5-yl]methyl]-4-(3,3,3-trifluoropropyl)-1,2,4-triazol-3-one	IC50	4.2 nM	US-9187466: Bisaryl-bonded aryltriazolones and use thereof
[1-(2-chlorophenyl)-2-[[2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetyl]amino]ethyl] carbamate	IC50	5 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
5H-1-benzazepin-5-ylidene acetamide, 10g	KI	6 nM
1N-{4-[16-ethyl-2,10-diazatetracyclo[11.2.1.02,12.04,9]hexadeca-4(9),5,7-trien-10-ylcarbonyl]phenyl}-2-phenylbenzamide	IC50	6 nM
5-(4-chlorophenyl)-2-[[1-(2-chlorophenyl)imidazol-4-yl]methyl]-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-3-one	IC50	6.5 nM	US-9687476: Bisaryl-bonded aryltriazolones and use thereof
5-(4-chlorophenyl)-2-[[3-(2-chlorophenyl)-1H-1,2,4-triazol-5-yl]methyl]-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-3-one	IC50	6.8 nM	US-9687476: Bisaryl-bonded aryltriazolones and use thereof
[2-[[2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetyl]amino]-1-(2,3-dichlorophenyl)ethyl] carbamate	IC50	7 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
benzazepine derivative, 34	IC50	7 nM
N-[2-(2-chlorophenyl)-2-(methanesulfonamido)ethyl]-2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetamide	IC50	8 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
[2-[[2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetyl]amino]-1-[2-(trifluoromethyl)phenyl]ethyl] carbamate	IC50	8 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
3-[[3-(4-chlorophenyl)-1-[[3-[(2,6-dichlorophenyl)methyl]-1H-1,2,4-triazol-5-yl]methyl]-5-oxo-1,2,4-triazol-4-yl]methyl]benzoic acid	IC50	8.6 nM	US-9187466: Bisaryl-bonded aryltriazolones and use thereof
5H-1-benzazepin-5-ylidene acetamide, 10f	KI	9.1 nM
5H-1-benzazepin-5-ylidene acetamide, 10b	KI	9.2 nM
[1-(2-chlorophenyl)-2-[[2-[3-(4-chlorophenyl)-4-[(2-fluorophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]acetyl]amino]ethyl] carbamate	IC50	10 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
1N-{4-[6-chloro-16-methyl-(12S)-2,10-diazatetracyclo[11.2.1.02,12.04,9]hexadeca-4(9),5,7-trien-10-ylcarbonyl]phenyl}-2-chlorobenzamide	IC50	10 nM
5H-1-benzazepin-5-ylidene acetamide, 10e	KI	11 nM
5H-1-benzazepin-5-ylidene acetamide, 10m	KI	11 nM
[2-(2-chlorophenyl)-3-[[2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetyl]amino]propyl] carbamate	IC50	12 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
2-[5-(2-chlorophenyl)-3-[[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]methyl]-1,2,4-triazol-1-yl]acetamide	IC50	12 nM	US-9687476: Bisaryl-bonded aryltriazolones and use thereof
tert-butyl N-[2-[[2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetyl]amino]-1-(2,3-dichlorophenyl)ethyl]carbamate	IC50	13 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
benzazepinelidene acetamide derivative, 1d	KI	13 nM
5H-1-benzazepin-5-ylidene acetamide, 1s	KI	13 nM
1N-{4-[6-chloro-16-ethyl-(12S)-2,10-diazatetracyclo[11.2.1.02,12.04,9]hexadeca-4(9),5,7-trien-10-ylcarbonyl]phenyl}-2-chlorobenzamide	IC50	13 nM
[1-(2-chlorophenyl)-2-[[2-[3-(4-chlorophenyl)-5-oxo-4-(3,3,3-trifluoropropyl)-1,2,4-triazol-1-yl]acetyl]amino]ethyl] carbamate	IC50	14 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
5H-1-benzazepin-5-ylidene acetamide, 10l	KI	14 nM
5H-1-benzazepin-5-ylidene acetamide, 1c	KI	15 nM
5H-1-benzazepin-5-ylidene acetamide, 10k	KI	16 nM
N-[2-(carbamoylamino)-2-(2-chlorophenyl)ethyl]-2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]acetamide	IC50	17 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
5-(4-chlorophenyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2-[[2-[2-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methyl]-1,2,4-triazol-3-one	IC50	17 nM	US-9187466: Bisaryl-bonded aryltriazolones and use thereof
benzazepinelidene acetamide derivative, 1f	KI	17 nM
benzazepine derivative, 20	IC50	17 nM
(2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino)-1-[(2’-methyl[1,1’-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide	KI	17 nM
tert-butyl N-[2-[[2-[3-(5-chlorothiophen-2-yl)-4-[(2-fluorophenyl)methyl]-5-oxo-1,2,4-triazol-1-yl]acetyl]amino]-1-[2-(trifluoromethyl)phenyl]ethyl]carbamate	IC50	18 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
5H-1-benzazepin-5-ylidene acetamide, 10d	KI	18 nM
2-[3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-1-yl]-N-[2-formamido-2-[3-(trifluoromethyl)phenyl]ethyl]acetamide	IC50	19 nM	US-9180120: Substituted N-phenethyltriazoloneacetamides and use thereof
5-(4-chlorophenyl)-2-[[3-[(2-chlorophenyl)methyl]-1H-1,2,4-triazol-5-yl]methyl]-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-1,2,4-triazol-3-one	IC50	19 nM	US-9187466: Bisaryl-bonded aryltriazolones and use thereof
3-chloro-4-[16-ethyl-(12S)-2,10-diazatetracyclo[11.2.1.02,12.04,9]hexadeca-4(9),5,7-trien-10-ylcarbonyl]-1-(3-fluoro-5-methylphenylcarboxamido)benzene	IC50	19 nM
5H-1-benzazepin-5-ylidene acetamide, 10h	KI	20 nM
5H-1-benzazepin-5-ylidene acetamide, 10c	KI	21 nM
5H-1-benzazepin-5-ylidene acetamide, 1i	KI	22 nM

ChEMBL bioactivities

1210 potent at pChembl≥5 of 1279 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	EC50	0.05	nM	VASOPRESSIN
10.30	EC50	0.05	nM	CHEMBL435323
10.30	EC50	0.05012	nM	VASOPRESSIN
10.28	EC50	0.052	nM	VASOPRESSIN
10.10	EC50	0.08	nM	CHEMBL4454891
10.00	EC50	0.1	nM	CHEMBL4528032
9.96	EC50	0.11	nM	CHEMBL4536454
9.85	EC50	0.14	nM	CHEMBL4532363
9.77	EC50	0.17	nM	CHEMBL4472007
9.72	EC50	0.19	nM	CHEMBL4459424
9.72	EC50	0.19	nM	CHEMBL4444891
9.70	EC50	0.2	nM	DESMOPRESSIN
9.70	EC50	0.2	nM	CHEMBL4571464
9.70	IC50	0.2	nM	CHEMBL102311
9.59	EC50	0.26	nM	CHEMBL4555263
9.57	EC50	0.27	nM	CHEMBL4451692
9.54	EC50	0.29	nM	CHEMBL4462616
9.52	EC50	0.3	nM	CHEMBL4439313
9.49	EC50	0.32	nM	CHEMBL4527761
9.46	EC50	0.35	nM	CHEMBL4521602
9.44	Ki	0.36	nM	CONIVAPTAN
9.37	Ki	0.43	nM	TOLVAPTAN
9.35	EC50	0.45	nM	CHEMBL4436571
9.35	EC50	0.4467	nM	ORNIPRESSIN
9.35	EC50	0.45	nM	ORNIPRESSIN
9.30	IC50	0.5	nM	CHEMBL311931
9.30	Ki	0.5	nM	CHEMBL2371605
9.28	Ki	0.53	nM	CHEMBL6101825
9.24	Ki	0.57	nM	CHEMBL603708
9.24	IC50	0.57	nM	CHEMBL603708
9.22	Ki	0.6	nM	PECAVAPTAN
9.22	Ki	0.6	nM	CONIVAPTAN
9.17	Ki	0.67	nM	CHEMBL445816
9.15	IC50	0.7	nM	CHEMBL49322
9.15	IC50	0.7	nM	CHEMBL420031
9.15	EC50	0.7	nM	CHEMBL363910
9.15	Ki	0.7	nM	CHEMBL6145092
9.15	Ki	0.7	nM	CHEMBL6103295
9.15	Ki	0.7	nM	CHEMBL2371604
9.13	EC50	0.74	nM	CHEMBL363910
9.10	Ki	0.8	nM	CHEMBL6103298
9.08	Ki	0.83	nM	CHEMBL2172291
9.05	Ki	0.9	nM	CHEMBL543854
9.05	Ki	0.9	nM	CHEMBL6102315
9.02	IC50	0.95	nM	CHEMBL434654
9.01	EC50	0.98	nM	CHEMBL594026
9.00	IC50	1	nM	CHEMBL310416
9.00	IC50	1	nM	LIXIVAPTAN
9.00	IC50	1	nM	CHEMBL3924331
9.00	Ki	1	nM	TOLVAPTAN

PubChem BioAssay actives

1045 with measured affinity, of 3058 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
Tolvaptan	1720599: Antagonist activity at human AVPR2 by PathHunter beta-arrestin assay	ic50	<0.0001	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2S)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S,4R)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2S)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(4R)-3-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-12-[(4-fluorophenyl)methyl]-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-N-[(2R)-1-[(2-amino-2-oxoethyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
vasopressin	1178647: Agonist activity at human vasopressin V2 expressed in HEK293 cells after 5 hrs by firefly luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0001	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S,4R)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(cyclopropylmethylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(cyclopropylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(propylamino)pentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(benzylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S)-N-(4-aminobutyl)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(2S,4R)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(2-thiophen-2-ylethylamino)pentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0002	uM
2-methoxy-N-[4-(spiro[3,5-dihydro-2H-1-benzazepine-4,3’-cyclohexene]-1-carbonyl)phenyl]benzamide	217704: In vitro inhibitory concentration against [3H]AVP binding to cloned human vasopressin receptor	ic50	0.0002	uM
Desmopressin	1178647: Agonist activity at human vasopressin V2 expressed in HEK293 cells after 5 hrs by firefly luciferase reporter gene assay	ec50	0.0002	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(methylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2S)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-13-(thiophen-2-ylmethyl)-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-hydroxyphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(benzylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(benzylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(diethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S,4R)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-12-benzyl-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]-4-hydroxypyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-1-(butylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(propylamino)pentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[4-(diaminomethylideneamino)butyl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(4S,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1-thia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(2-methylpropylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(4R)-3-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-12-[(4-fluorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(2-thiophen-2-ylethylamino)pentan-2-yl]-1,3-thiazolidine-4-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-ethylphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0003	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-chlorophenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-oxo-1-(propan-2-ylamino)pentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0004	uM
(2S)-1-[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-16-[(4-chlorophenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-(ethylamino)-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0004	uM
(2S)-N-[(2S)-5-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	613481: Agonist activity at recombinant human vasopressin V2 receptor expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0004	uM
N-[4-(2-methyl-4,5-dihydro-3H-imidazo[4,5-d][1]benzazepine-6-carbonyl)phenyl]-2-phenylbenzamide	483982: Displacement [3H]Arg human recombinant Vasopressin V2 receptor	ki	0.0004	uM
(2S)-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-15-[(4-methylphenyl)methyl]-5,8,11,14,17-pentaoxo-9-propan-2-yl-12-(thiophen-2-ylmethyl)-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]-N-[(2R)-5-(diaminomethylideneamino)-1-hydroxypentan-2-yl]pyrrolidine-2-carboxamide	1598498: Agonist activity at recombinant human V2 receptor expressed in HEK293 cells measured after 5 hrs by cAMP response element driven luciferase reporter gene assay	ec50	0.0004	uM
N-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-2,3-dimethylbenzamide	217845: Displacement of [3H]AVP from human V2 receptor expressed in murine fibroblast cell line (LV2) membranes	ic50	0.0005	uM
(10S,13R,16S,19R,22S)-N-[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-13-(2-amino-2-oxoethyl)-19-benzyl-22-[(4-ethoxyphenyl)methyl]-12,15,18,21,24-pentaoxo-16-propan-2-yl-7,8-dithia-11,14,17,20,23-pentazaspiro[5.19]pentacosane-10-carboxamide	217852: Binding affinity of compound towards Vasopressin receptor by binding [3H]LVP to dog renal medullary preparation.	ki	0.0005	uM

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
antibiotic G 418	increases activity, increases expression	2
Cyclic AMP	affects binding, increases abundance, increases activity	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetamides	increases activity, affects binding	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	decreases expression	1
Deamino Arginine Vasopressin	affects binding, increases activity	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Endocannabinoids	increases activity, increases reaction, affects binding	1

ChEMBL screening assays

309 unique, capped per target: 208 binding, 100 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009070	Binding	Displacement of [3H]vasopressin from human V2 receptor expressed in CHO cells	Synthesis and structure-activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetic acid as selective arginine vasopressin V2 receptor agonists. — Bioorg Med Chem
CHEMBL1015239	Functional	Agonist activity at human vasopressin V2 receptor expressed in HEK293 cells assessed as increase in intracellular cAMP level by CRE-luciferase reporter gene assay	New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists. — J Med Chem
CHEMBL4325235	ADMET	Agonist activity at recombinant human V2 receptor expressed in CHOK1 cells assessed as increase in cAMP level measured after 30 mins by HTRF assay	Engineering a Potent, Long-Acting, and Periphery-Restricted Oxytocin Receptor Agonist with Anorexigenic and Body Weight Reducing Effects. — J Med Chem

Cellosaurus cell lines

8 cell lines: 4 spontaneously immortalized cell line, 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0S8	ACTOne AVPR2	Transformed cell line	Female
CVCL_H509	CHO-K1/V2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU81	cAMP Hunter CHO-K1 AVPR2 Gs	Spontaneously immortalized cell line	Female
CVCL_KW36	PathHunter CHO-K1 AVPR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ33	PathHunter HEK 293 AVPR2 beta-arrestin	Transformed cell line	Female
CVCL_KZ78	PathHunter U2OS AVPR2 Activated GPCR Internalization	Cancer cell line	Female
CVCL_YK31	U2OS AVPR2 cAMP-Nomad	Cancer cell line	Female
CVCL_ZI81	GeneBLAzer AVPR2-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05190744	PHASE2	COMPLETED	Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT00478335	Not specified	COMPLETED	Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus
NCT04939753	Not specified	COMPLETED	Nephrogenic Diabetes Insipidus During Prolonged Sevoflurane Sedation in the ICU: a Retrospective Analysis
NCT05307042	Not specified	UNKNOWN	Decline in Renal Concentration Ability in Lithium Treated Patients
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06604975	Not specified	NOT_YET_RECRUITING	Arginin-stimulated Copeptin in Polyuria-polydipsia Syndrome in Children