VIPR1

Summary

VIPR1 (vasoactive intestinal peptide receptor 1, HGNC:12694) is a protein-coding gene on chromosome 3p22.1, encoding Vasoactive intestinal polypeptide receptor 1 (P32241). G protein-coupled receptor activated by the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (ADCYAP1/PACAP).

This gene encodes a receptor for vasoactive intestinal peptide, a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7433 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 99 total
• GTEx eGene: eQTL in 23 tissues, sQTL in 6 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.34 (unconstrained)
• MANE Select transcript: NM_004624
• Notable: 99 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12694
Approved symbol	VIPR1
Name	vasoactive intestinal peptide receptor 1
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	VPAC1, RDC1, HVR1, VPAC1R
Ensembl gene	ENSG00000114812
Ensembl biotype	protein_coding
OMIM	192321
Entrez	7433

Gene structure

Transcript identifiers

Ensembl transcripts: 60 — 27 nonsense_mediated_decay, 26 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000325123

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 4, TSL 3: 6, TSL 5: 4

ENST00000325123, ENST00000433647, ENST00000436487, ENST00000439731, ENST00000439910, ENST00000443646, ENST00000446673, ENST00000450274, ENST00000465338, ENST00000473495, ENST00000473575, ENST00000487545, ENST00000490161, ENST00000495189, ENST00000498102, ENST00000883016, ENST00000883017, ENST00000883018, ENST00000883019, ENST00000883020, ENST00000883021, ENST00000883022, ENST00000883023, ENST00000883024, ENST00000883025, ENST00000883026, ENST00000883027, ENST00000883028, ENST00000883029, ENST00000883030, ENST00000913982, ENST00000954072, ENST00000954073, ENST00001000200, ENST00001000201, ENST00001000202, ENST00001000204, ENST00001000205, ENST00001000207, ENST00001000208, ENST00001000209, ENST00001000211, ENST00001000212, ENST00001000213, ENST00001000214, ENST00001000215, ENST00001000216, ENST00001000217, ENST00001000218, ENST00001000219, ENST00001000220, ENST00001010207, ENST00001010208, ENST00001010209, ENST00001010210, ENST00001010211, ENST00001010212, ENST00001010213, ENST00001116627, ENST00001140260

RefSeq mRNA: 5 — MANE Select: NM_004624 NM_001251882, NM_001251883, NM_001251884, NM_001251885, NM_004624

CCDS: CCDS2698, CCDS58828

Canonical transcript exons

ENST00000325123 — 13 exons

Exon	Start	End
ENSE00003460096	42519223	42519330
ENSE00003464487	42535343	42535384
ENSE00003488172	42530779	42530932
ENSE00003505964	42531471	42531531
ENSE00003516247	42527991	42528123
ENSE00003521687	42531803	42531869
ENSE00003527672	42534975	42535104
ENSE00003586884	42513749	42513854
ENSE00003601410	42532242	42532333
ENSE00003663519	42525887	42525993
ENSE00003790864	42527393	42527496
ENSE00003842902	42536090	42537568
ENSE00003843166	42502643	42502813

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 99.61.

FANTOM5 (CAGE): breadth broad, TPM avg 8.0133 / max 353.2848, expressed in 861 samples.

Highest expression (Bgee): lung, upper lobe of left lung, upper lobe of lung, mucosa of transverse colon, rectum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

VIPR1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 29 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	1.2e-14	+0.66	3:42488258:C:T
Nerve Tibial	eqtl	8.2e-08	+0.19	3:42479492:A:G
Whole Blood	eqtl	1.7e-07	+0.21	3:42527208:C:G
Brain Frontal Cortex BA9	eqtl	3.2e-06	-0.19	3:42500395:A:G
Skin Sun Exposed Lower leg	eqtl	6.9e-06	-0.14	3:42476887:G:A
Adipose Visceral Omentum	eqtl	7.0e-05	-0.41	3:42496688:G:T
Brain Cortex	eqtl	1.0e-04	+0.19	3:42480411:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.3e-04	-0.14	3:42476887:G:A
Skin Sun Exposed Lower leg	sqtl	1.5e-04	-0.41	3:42512934:A:C
Esophagus Muscularis	eqtl	1.5e-04	+0.19	3:42483694:G:C
Brain Cerebellum	sqtl	2.9e-04	-0.66	3:42527208:C:G
Esophagus Gastroesophageal Junction	eqtl	4.6e-03	+0.19	3:42475653:A:G
Brain Cerebellum	eqtl	5.4e-03	-0.58	3:42418384:C:CTA
Testis	eqtl	5.7e-03	+0.23	3:42337048:T:C
Muscle Skeletal	eqtl	6.7e-03	+0.16	3:42480257:G:A
Brain Substantia nigra	eqtl	9.3e-03	+0.33	3:42488258:C:T
Brain Anterior cingulate cortex BA24	eqtl	1.3e-02	+0.22	3:42524661:G:A
Pancreas	eqtl	1.5e-02	+0.96	3:41555424:C:T
Adipose Subcutaneous	eqtl	2.5e-02	-0.46	3:42610946:A:G
Small Intestine Terminal Ileum	sqtl	2.7e-02	+2.80	3:43250817:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
36257	8.0133	861

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.61	gold quality
upper lobe of left lung	UBERON:0008952	97.34	gold quality
upper lobe of lung	UBERON:0008948	97.04	gold quality
mucosa of transverse colon	UBERON:0004991	95.38	gold quality
rectum	UBERON:0001052	94.19	gold quality
ileal mucosa	UBERON:0000331	93.76	gold quality
skin of leg	UBERON:0001511	93.25	gold quality
skin of abdomen	UBERON:0001416	92.60	gold quality
duodenum	UBERON:0002114	92.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.15	gold quality
lung	UBERON:0002048	91.53	gold quality
minor salivary gland	UBERON:0001830	91.44	gold quality
cerebellar hemisphere	UBERON:0002245	91.21	gold quality
cerebellar cortex	UBERON:0002129	91.07	gold quality
lower lobe of lung	UBERON:0008949	91.05	silver quality
zone of skin	UBERON:0000014	90.78	gold quality
transverse colon	UBERON:0001157	90.58	gold quality
granulocyte	CL:0000094	89.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.43	gold quality
right frontal lobe	UBERON:0002810	89.42	gold quality
jejunal mucosa	UBERON:0000399	89.30	gold quality
cerebellum	UBERON:0002037	88.99	gold quality
right lobe of liver	UBERON:0001114	88.95	gold quality
small intestine	UBERON:0002108	88.81	gold quality
saliva-secreting gland	UBERON:0001044	88.53	gold quality
colonic mucosa	UBERON:0000317	88.24	gold quality
mouth mucosa	UBERON:0003729	88.23	gold quality
prostate gland	UBERON:0002367	87.35	gold quality
monocyte	CL:0000576	86.94	gold quality
leukocyte	CL:0000738	86.87	gold quality
mononuclear cell	CL:0000842	86.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.73	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.55	gold quality
left lobe of thyroid gland	UBERON:0001120	86.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.41	gold quality
prefrontal cortex	UBERON:0000451	86.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.29	gold quality
right lobe of thyroid gland	UBERON:0001119	85.18	gold quality
upper arm skin	UBERON:0004263	85.17	gold quality
nucleus accumbens	UBERON:0001882	84.73	gold quality
frontal cortex	UBERON:0001870	84.58	gold quality
thyroid gland	UBERON:0002046	84.24	gold quality
liver	UBERON:0002107	84.08	gold quality
adult organism	UBERON:0007023	84.08	gold quality
upper leg skin	UBERON:0004262	84.05	silver quality
intestine	UBERON:0000160	83.75	gold quality
right coronary artery	UBERON:0001625	83.43	gold quality
cingulate cortex	UBERON:0003027	83.42	gold quality
anterior cingulate cortex	UBERON:0009835	83.16	gold quality
neocortex	UBERON:0001950	82.98	gold quality
adipose tissue	UBERON:0001013	82.77	gold quality
blood	UBERON:0000178	82.57	gold quality
large intestine	UBERON:0000059	82.23	gold quality
colonic epithelium	UBERON:0000397	82.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.97	gold quality
colon	UBERON:0001155	81.94	gold quality
omental fat pad	UBERON:0010414	81.89	gold quality
peritoneum	UBERON:0002358	81.82	gold quality
nasal cavity epithelium	UBERON:0005384	81.70	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	81.61	gold quality
orbitofrontal cortex	UBERON:0004167	81.49	gold quality
Brodmann (1909) area 46	UBERON:0006483	81.33	gold quality
connective tissue	UBERON:0002384	81.31	gold quality
popliteal artery	UBERON:0002250	81.22	gold quality
tibial artery	UBERON:0007610	81.18	gold quality
type B pancreatic cell	CL:0000169	80.78	gold quality
gall bladder	UBERON:0002110	80.66	gold quality
left coronary artery	UBERON:0001626	80.63	gold quality
cerebral cortex	UBERON:0000956	80.53	gold quality
right atrium auricular region	UBERON:0006631	80.44	gold quality
coronary artery	UBERON:0001621	80.30	gold quality
Brodmann (1909) area 10	UBERON:0013541	80.15	gold quality
body of stomach	UBERON:0001161	79.75	gold quality
telencephalon	UBERON:0001893	79.51	gold quality
olfactory bulb	UBERON:0002264	79.31	gold quality
nasal cavity mucosa	UBERON:0001826	79.16	gold quality
pancreatic ductal cell	CL:0002079	79.11	silver quality
superior frontal gyrus	UBERON:0002661	78.85	gold quality
cardiac atrium	UBERON:0002081	78.67	gold quality
urethra	UBERON:0000057	78.57	gold quality
caudate nucleus	UBERON:0001873	78.34	gold quality
primary visual cortex	UBERON:0002436	78.30	gold quality
aorta	UBERON:0000947	78.27	gold quality
hair follicle	UBERON:0002073	78.24	gold quality
urinary bladder	UBERON:0001255	78.20	gold quality
jejunum	UBERON:0002115	78.03	gold quality
lymph node	UBERON:0000029	77.87	gold quality
brain	UBERON:0000955	77.72	gold quality
esophagus mucosa	UBERON:0002469	77.56	gold quality
postcentral gyrus	UBERON:0002581	77.37	gold quality
forebrain	UBERON:0001890	77.26	gold quality
central nervous system	UBERON:0001017	77.23	gold quality
occipital lobe	UBERON:0002021	77.16	gold quality
spleen	UBERON:0002106	77.01	gold quality
anatomical system	UBERON:0000467	76.89	gold quality
apex of heart	UBERON:0002098	76.86	gold quality
multicellular organism	UBERON:0000468	76.85	gold quality
vermiform appendix	UBERON:0001154	76.85	gold quality
vagina	UBERON:0000996	76.84	gold quality
material anatomical entity	UBERON:0000465	76.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	14.27
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Lung	tissue	37.6	medium
Duodenum	tissue	32.4	medium
Cerebral cortex	tissue	29.0	low
Insular cortex	tissue	29.0
Small intestine	tissue	28.2	medium
Temporal cortex	tissue	27.0
Prefrontal cortex	tissue	26.9
Retrosplenial and cingulate cortex	tissue	26.8
Colon	tissue	26.3	medium
Retrosplenial cortex	tissue	26.2
Rectum	tissue	26.1	medium
Motor cortex	tissue	25.6
Hippocampal formation	tissue	24.5
Entorhinal cortex	tissue	24.5
Somatosensory cortex	tissue	24.4
Occipital cortex	tissue	23.9
Liver	tissue	23.1	low
Amygdala	tissue	21.6
Olfactory bulb	tissue	20.4
Postcentral gyrus	tissue	20.0
Cerebellum	tissue	18.2	medium
Prostate	tissue	18.2	high
Skin 1	tissue	17.1	medium
Corpus callosum	tissue	16.7
Nucleus accumbens	tissue	16.5
Ventral forebrain	tissue	15.9
Basal ganglia	tissue	14.5	low
Septum	tissue	14.2
Adipose tissue	tissue	13.0	low
Periaqueductal gray	tissue	12.5
Putamen	tissue	12.2
Salivary gland	tissue	11.6	medium
Hypothalamus	tissue	11.4
Substantia nigra	tissue	10.8
Spinal cord	tissue	10.0
Medulla oblongata	tissue	9.9
Midbrain	tissue	9.8
Thalamus	tissue	9.3
Superior colliculi	tissue	9.1
Breast	tissue	8.8	medium
Seminal vesicle	tissue	8.4	medium
Pons	tissue	8.3
Frontal cortex	tissue	8.0
Hippocampus	tissue	6.4	low
Epididymis	tissue	6.2	medium
Gallbladder	tissue	5.6	medium
Stomach 1	tissue	5.4	medium
Urinary bladder	tissue	4.9	medium
Vagina	tissue	4.7	medium
Thyroid gland	tissue	4.6	medium
Tongue	tissue	4.5
Caudate putamen	tissue	4.5
Lymph node	tissue	4.3	medium
Spleen	tissue	4.1	low
Retina	tissue	3.9
Parathyroid gland	tissue	3.9	medium
Appendix	tissue	3.2	medium
Esophagus	tissue	3.1	medium
Choroid plexus	tissue	3.0
Heart muscle	tissue	2.8	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Temporo-occipital transitional zone (23.9), Posterior insular cortex (21.5), Transversal temporal gyrus, anterior (21.1), Superior temporal gyrus (20.9), Transversal temporal gyrus, posterior (20.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, IKZF1, NEUROD4, NR1H4

miRNA regulators (miRDB)

Targeting VIPR1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 64 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-508-5P	99.41	64.25	1248

Functional genomics

gnomAD constraint: pLI 1.62e-23, LOEUF 1.34, missense Z -0.636 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000325123 — one region, missense o/e 1.04.

Literature-anchored findings (GeneRIF, showing 40)

• Vasoactive intestinal peptide receptor-1 (VPAC-1) is a novel gene target of the hemolymphopoietic transcription factor Ikaros. (PMID:11812772)
• VPAC1 is a cellular neuroendocrine receptor expressed on T cells that actively facilitates productive HIV-1 infection. (PMID:11834941)
• Thus, the highly diverged chemical properties of the hydrophobic “YL” motif and charged “DR(Y)” motif could be a crucial difference between the Secretin Receptor Family and the Rhodopsin Family with respect to receptor activation and G-protein coupling. (PMID:11859928)
• VPAC1 receptor mRNA is expressed in the trigeminal, otic and superior cervical ganglia (prejunctional) and cerebral arteries (postjunctional). (PMID:11930171)
• a small sequence in the third intracellular loop of the VPAC(1) receptor is responsible for the efficient agonist-stimulated intracellular calcium concentration increase (PMID:11981043)
• Genetic complexity of HVR1 quasispecies of hepatitis C virus in patients with cirrhosis. (PMID:12094871)
• a selective filter; Identification of a critical domain for restricting secretin binding (PMID:12133828)
• Vasoactive intestinal peptide (VIP) inhibits the proliferation of bone marrow progenitors through the VPAC1 receptor. (PMID:12225791)
• the role of charged residues in the intracellular loop 3 and the proximal C-terminal tail of hVPAC1 receptor for agonist-induced adenylyl cyclase activation (PMID:12690118)
• cloning and sequencing of 5’ flanking region; VPAC1 may play a functional role in development of both cerebellum and adrenal medulla (PMID:14599709)
• Data suggest that vasoactive intestinal peptide directly stimulates cortisol secretion from H295 cells via activation of the VPAC1 receptor subtype. (PMID:15171718)
• the hVPAC1 receptor binds to vasoactive intestinal peptide at its N-terminal ectodomain (PMID:15247290)
• Interaction of different G proteins with the recombinant VPAC1 receptor involves different receptor sub-domains. (PMID:15451021)
• the VPAC1 receptor carboxyl terminus has a role in agonist-induced receptor phosphorylation, internalization, and recycling (PMID:15932876)
• Farnesoid X receptor agonists may increase gallbladder fluid secretion through transcriptional activation of VPAC1. (PMID:16037943)
• analysis of the two-step activation mechanism of VPAC receptor and of class II G protein-coupled receptors (PMID:16520374)
• Thr429 phosphorylation has a role in activation of human VPAC1 (PMID:16554109)
• 125I-[Bpa28-vasoactive intestinal peptide] was covalently bonded to the 121-133 fragment within the N-terminal ectodomain of the receptor (PMID:16888162)
• Photoaffinity experiments clearly indicated that the 6-28 part of VIP physically interacts with the N-terminal ectodomain of VPAC1 receptor (PMID:16888167)
• MCF-7 cells have VPAC1 receptors that bound the VIP chemotherapeutic conjugate (PMID:16888206)
• observations provide additional evidence for a role of proapoptotic caspase adaptor protein and PAC1 R in the events determining the outcome of prostate cancer (PMID:16888207)
• identification and characterization of novel five-transmembrane(5TM) isoforms of VPAC1 (PMID:16934434)
• expression of VIP receptor-1 (VPAC1) and VPAC2 in CD4+ T cells changed reciprocally in the context of the activation state (PMID:17077178)
• The differential expression of VIPR1 in ulcerative colitis and Crohn’s disease mucosa suggests that the VIP system plays different roles in the pathogenesis of inflammatory bowel disease. (PMID:17611633)
• Both intra- and extracellular Ca2+ play a role in controlling pro-inflammatory functions stimulated by PACAP which acts through a VPAC-1, FPRL1/Galphai/PI3K/ERK pathway and a VPAC-1/Galphas/PKA/p38 pathway to fully activate monocytes (PMID:17651798)
• analysis of VIP 16gamma-glutamyl diamino derivative positive charges on hVPAC1 and hVPAC2 receptor function (PMID:17883247)
• Structural studies provide a detailed molecular understanding of the VIP-VPAC1 receptor interaction. (PMID:17885205)
• VPAC1 signaling tempers normal megakaryopoiesis, and inhibition of this pathway stimulates megakaryocyte differentiation. (PMID:18000164)
• Proinflammatory effect of VIP is mediated via the specific G protein-coupled receptor VIP/pituitary adenylate cyclase-activating protein (VPAC1) receptor as well as via FPRL1. (PMID:18174366)
• VIP and PACAP levels were decreased in anterior vaginal wall of stress urinary incontinence and pelvic organ prolapse patients,they may participate in the pathophysiology of these diseases. (PMID:18351280)
• deficient expression of VPAC1 (vasoactive intestinal peptide receptor 1) in immune cells of Rheumatoid Arthritis was associated with the predominant proinflammatory Th1 mileu; reduced VPAC1 expression in RA is associated with genetic polymorphism (PMID:18383379)
• Results indicate that the N-terminal part of VIP physically interacts with the N-ted in the continuity of 6-28 VIP sequence; and the N-terminal part of VIP and its antagonist (PG97-269) have different sites of interaction with the VPAC1 receptor N-ted. (PMID:18597186)
• VIP acts in an autocrine fashion via VPAC1 to inhibit megakaryocyte proliferation and induce proplatelet formation (PMID:18663606)
• HLA-B (*)2705 and a functional polymorphism in VIPR1 gene, might be due to a founder effect or might be the result of a selective pressure. Consequent downregulation of this receptor in presence of a ‘danger’ signal might influence susceptibility to AS. (PMID:18668120)
• Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype of VIPR1 distribution of snps (PMID:19309439)
• We describe significant upregulation of the SPP1 gene, downregulation of VIPR1, and losses of the VIPR1 gene. (PMID:20014941)
• Results indicate that VPAC1, but not VPAC2 or PAC1, up-regulation in macrophages is a common mechanism in response to acute and chronic pro-inflammatory stimuli. (PMID:20026142)
• Moreover, we report the markedly nuclear localization of VPAC(1) receptors in estrogen-dependent (T47D) and independent (MDA-MB-468) human breast cancer cell lines (PMID:20691743)
• role of in MicroRNA 525-5p down-modulating VPAC1 expressio (PMID:20706588)
• The VIPR1 polymorphism, previously linked to gastrointestinal dysmotility disorders, does not represent a common risk factor for gallstones in the general or in an elderly population. (PMID:20922191)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vipr1b	ENSDARG00000059058
mus_musculus	Vipr1	ENSMUSG00000032528
rattus_norvegicus	Vipr1	ENSRNOG00000047457

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), EVA1C (ENSG00000166979), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177), ADGRG1 (ENSG00000205336), GCGR (ENSG00000215644)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:109272) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 20 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, incomplete penetrance	2
hypoglycemia	1
abnormal intestine morphology	1
decreased body weight	1
ataxia	1
decreased locomotor activity	1
impaired coordination	1
abnormal gait	1
hunched posture	1
postnatal growth retardation	1
abnormal glucose homeostasis	1
increased insulin sensitivity	1
intestinal obstruction	1
abnormal exocrine pancreas morphology	1
impaired glucose tolerance	1
abnormal enterocyte proliferation	1
disorganized pancreatic islets	1
enlarged cecum	1
lethality at weaning, incomplete penetrance	1
small intestine hemorrhage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	Q76LL8	99.5%	Diamond
Pongo abelii	Q5RAQ1	98.5%	Diamond
Canis lupus familiaris	Q9TU31	95.3%	Diamond
Sus scrofa	P50133	95.1%	Diamond
Bos taurus	Q1LZF7	95.1%	Diamond
Ovis aries	O62772	94.9%	Diamond
Gallus gallus	Q90812	89.8%	Diamond
Oncorhynchus gorbuscha	Q8AXU4	86.6%	Diamond
Paralichthys olivaceus	Q9IB86	86.0%	Diamond
Cavia porcellus	O08893	85.6%	Diamond
Mesocricetus auratus	P43218	84.6%	Diamond
Xenopus laevis	O42602	82.6%	Diamond
Oryctolagus cuniculus	O46502	80.4%	Diamond
Didelphis virginiana	P25107	79.4%	Diamond
Meleagris gallopavo	Q91085	70.3%	Diamond
Carassius auratus	Q90308	65.2%	Diamond
Manduca sexta	P35464	53.6%	Diamond
Acheta domesticus	Q16983	53.6%	Diamond
Drosophila melanogaster	Q9W4Y2	39.8%	Diamond
Caenorhabditis elegans	P30650	31.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
VIPR1-AS1	ncRNA	100874007
LYZL4	protein-coding	131375
ZBTB47-AS1	ncRNA	101928323
NKTR	protein-coding	4820
SS18L2	protein-coding	51188
SEC22C	protein-coding	9117
KLHL40	protein-coding	131377
ZBTB47	protein-coding	92999

Protein

Protein identifiers

Vasoactive intestinal polypeptide receptor 1 — P32241 (reviewed: P32241)

Alternative names: Pituitary adenylate cyclase-activating polypeptide type II receptor, VPAC1 receptor

All UniProt accessions (4): C9JDT8, C9JH33, P32241, F2Z2U6

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor activated by the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (ADCYAP1/PACAP). Binds VIP and both PACAP27 and PACAP38 bioactive peptides with the following order of ligand affinity VIP = PACAP27 > PACAP38. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. Activates cAMP-dependent pathway.

Subunit / interactions. Interacts with ADCYAP1/PACAP; activated by both PACAP27 and PACAP38 neuropeptides. Interacts with VIP; the interaction results in VIPR1 activation.

Subcellular location. Cell membrane.

Tissue specificity. In lung, HT-29 colonic epithelial cells, Raji B-lymphoblasts. Lesser extent in brain, heart, kidney, liver and placenta. Not expressed in CD4+ or CD8+ T-cells. Expressed in the T-cell lines HARRIS, HuT 78, Jurkat and SUP-T1, but not in the T-cell lines Peer, MOLT-4, HSB and YT.

Similarity. Belongs to the G protein-coupled receptor 2 family.

Isoforms (5)

UniProt ID	Names	Canonical?
P32241-1	Short, hIVR8	yes
P32241-2	Long, hIVR5
P32241-3	3
P32241-4	4
P32241-5	5

RefSeq proteins (5): NP_001238811, NP_001238812, NP_001238813, NP_001238814, NP_004615* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000832	GPCR_2_secretin-like	Family
IPR001571	GPCR_2_VIP_rcpt	Family
IPR001771	GPCR_2_VIP_rcpt_1	Family
IPR001879	GPCR_2_extracellular_dom	Domain
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR050332

Pfam: PF00002, PF02793

UniProt features (68 total): helix 21, topological domain 8, transmembrane region 7, strand 7, disulfide bond 5, splice variant 5, glycosylation site 4, sequence conflict 4, sequence variant 2, turn 2, signal peptide 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

17 structures by resolution:

PDB	Title	Method	Resolution (Å)
5IB2	Crystal structure of HLA-B*27:05 complexed with the self-peptide pVIPR	X-RAY DIFFRACTION	1.44
1OGT	CRYSTAL STRUCTURE OF HLA-B*2705 COMPLEXED WITH THE VASOACTIVE INTESTINAL PEPTIDE TYPE 1 …	X-RAY DIFFRACTION	1.47
5DEF	Crystal structure of B*27:04 complex bound to the pVIPR peptide	X-RAY DIFFRACTION	1.6
3B6S	Crystal Structure of hla-b*2705 Complexed with the Citrullinated Vasoactive Intestinal …	X-RAY DIFFRACTION	1.8
7ALO	Structure of B*27:09/photoRL9	X-RAY DIFFRACTION	1.8
5DEG	Crystal structure of B*27:06 bound to the pVIPR peptide	X-RAY DIFFRACTION	1.83
3B3I	Citrullination-dependent differential presentation of a self-peptide by HLA-B27 subtypes	X-RAY DIFFRACTION	1.86
5IB1	Crystal structure of HLA-B*27:05 complexed with the self-peptide pVIPR measured at 295 K	X-RAY DIFFRACTION	1.91
5IB3	Crystal structure of HLA-B*27:05 complexed with the self-peptide pVIPR and Copper	X-RAY DIFFRACTION	1.91
3HCV	Crystal structure of HLA-B*2709 complexed with the double citrullinated vasoactive …	X-RAY DIFFRACTION	1.95
5IB4	Crystal structure of HLA-B*27:05 complexed with the self-peptide pVIPR and Nickel	X-RAY DIFFRACTION	1.95
3DTX	Crystal structure of HLA-B*2705 complexed with the double citrullinated vasoactive …	X-RAY DIFFRACTION	2.1
1OF2	Crystal structure of HLA-B*2709 complexed with the vasoactive intestinal peptide type 1 …	X-RAY DIFFRACTION	2.2
8E3Y	Cryo-EM structure of the VPAC1R-PACAP27-Gs complex	ELECTRON MICROSCOPY	2.3
5IB5	Crystal structure of HLA-B*27:09 complexed with the self-peptide pVIPR and Copper	X-RAY DIFFRACTION	2.49
8E3Z	Cryo-EM structure of the VPAC1R-VIP-Gs complex	ELECTRON MICROSCOPY	2.7
6VN7	Cryo-EM structure of an activated VIP1 receptor-G protein complex	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32241-F1	76.72	0.30

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 6VN7, 8E3Y, 8E3Z

Human Protein Atlas

Protein class: Transporters, G-protein coupled receptors, GPCRs excl olfactory receptors, Family 2 (B) receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

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

Disulfide bonds (5)

Type	Positions
Disulfide bond	37–208, 50–72, 63–105, 86–122, 215–285

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	58, 69, 100, 290

Mutagenesis-validated functional residues (1)

Position	Phenotype
139	decreased adcyap1/pacap27 potency for vipr1.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-373080	Class B/2 (Secretin family receptors)	—
R-HSA-418555	G alpha (s) signalling events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-420092	Glucagon-type ligand receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 214 (showing top): MODULE_92, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, MODULE_274, MODULE_64, MODULE_329, PID_REG_GR_PATHWAY, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MODULE_75, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, MODULE_206, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, CAIRO_HEPATOBLASTOMA_DN, chr3p22, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, NAKAYAMA_SOFT_TISSUE_TUMORS_PCA2_DN

GO Biological Process (7): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of cell population proliferation (GO:0008284), signal transduction (GO:0007165)

GO Molecular Function (7): pituitary adenylate cyclase-activating polypeptide receptor activity (GO:0001634), vasoactive intestinal polypeptide receptor activity (GO:0004999), G protein-coupled peptide receptor activity (GO:0008528), peptide hormone binding (GO:0017046), transmembrane signaling receptor activity (GO:0004888), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class B/2 (Secretin family receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

23 GO namespaces:

Category	Terms
G protein-coupled receptor activity	4
G protein-coupled receptor signaling pathway	3
signal transduction	2
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
peptide receptor activity	1
hormone binding	1
signaling receptor activity	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
protein-containing complex	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	BP	direct assay
adenylate cyclase-activating G protein-coupled receptor signaling pathway	BP	direct assay
plasma membrane	CC	direct assay
signaling receptor complex	CC	direct assay
peptide hormone binding	MF	physical interaction
pituitary adenylate cyclase-activating polypeptide receptor activity	MF	direct assay
vasoactive intestinal polypeptide receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 860 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VIPR1	VIP	P01282	970
VIPR1	ADCYAP1	P18509	938
VIPR1	SCT	P09683	759
VIPR1	HTR1D	P28221	691
VIPR1	ADORA1	P30542	678
VIPR1	ERV3-1	Q14264	613
VIPR1	ERVFRD-1	P60508	612
VIPR1	ATG5	Q9H1Y0	608
VIPR1	GCG	P01275	592
VIPR1	ADORA2A	P29274	592
VIPR1	ERVW-1	Q9UQF0	526
VIPR1	GHRH	P01286	520
VIPR1	ADA	P00813	499
VIPR1	RAMP1	O60894	498
VIPR1	PPIP5K2	O43314	494

IntAct

Human interaction partners of VIPR1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
PRDM5	physical association	0.560	3
HLA-A	direct interaction	0.440	1
VIP	physical association	0.400	2
CALM1	physical association	0.400	1
TINF2	physical association	0.370	1
GPR89A	association	0.350	2
ATP9A	association	0.350	1
SLC33A1	association	0.350	1

BioGRID (209 interactions; top human partners by supporting records): AGPAT4 (Affinity Capture-MS; 2 records), ARL6IP5 (Affinity Capture-MS; 2 records), ATP5B (Affinity Capture-MS; 2 records), ATP5F1 (Affinity Capture-MS; 2 records), ATP8 (Affinity Capture-MS; 2 records), DYM (Affinity Capture-MS; 2 records), GPR89A (Affinity Capture-MS; 2 records), KIAA1244 (Affinity Capture-MS; 2 records), MFSD5 (Affinity Capture-MS; 2 records), PTPLB (Affinity Capture-MS; 2 records), REEP6 (Affinity Capture-MS; 2 records), RNF13 (Affinity Capture-MS; 2 records), SC5D (Affinity Capture-MS; 2 records), SLC25A17 (Affinity Capture-MS; 2 records), SLC7A2 (Affinity Capture-MS; 2 records)

SIGNOR signaling

13 signaling interactions:

A	Effect	B	Mechanism
ADCYAP1	up-regulates	VIPR1	binding
VIP	up-regulates	VIPR1	binding
VIPR1	“up-regulates activity”	GNAI1	binding
VIPR1	“up-regulates activity”	GNAI2	binding
VIPR1	“up-regulates activity”	GNAZ	binding
VIPR1	“up-regulates activity”	GNA11	binding
VIPR1	“up-regulates activity”	GNA14	binding
VIPR1	“up-regulates activity”	GNA12	binding
VIPR1	“up-regulates activity”	GNAS	binding
VIPR1	“up-regulates activity”	GNAO1	binding
VIPR1	“up-regulates activity”	GNAQ	binding
VIPR1	“up-regulates activity”	GNA15	binding
VIPR1	“up-regulates activity”	GNA13	binding

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
VIPR1-VIPR2 complex	2	VIPR1, VIPR2
★ SCTR-VIPR1 complex	2	SCTR, VIPR1
★ RAMP1-VIPR1 complex	2	VIPR1, RAMP1
★ RAMP3-VIPR1 complex	2	VIPR1, RAMP3
★ RAMP2-VIPR1 complex	2	RAMP2, VIPR1

Ligand–receptor pairs (CellPhoneDB) (3)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ADCYAP1	receptor	Signaling by Pituitary adenylate
VIP	receptor	Signaling by Vasoactive Intestinal Peptide
SCT	receptor	Signaling by Secretin

Disease & clinical

Genetic variants

Variant evidence for VIPR1: 99 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	10
Benign	8

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 1,323):

Position(s)	Effect	Δscore	Sites
3:42513747–42513748	acceptor_loss	1.0000	5
3:42519221–42519222	acceptor_loss	1.0000	6
3:42519331–42519332	donor_loss	1.0000	4
3:42527497–42527498	donor_loss	1.0000	5
3:42530777–42530778	acceptor_loss	1.0000	6
3:42530898	donor_gain	1.0000
3:42535341–42535342	acceptor_loss	1.0000	5
3:42536088–42536089	acceptor_loss	1.0000	6
3:42502814–42502815	donor_loss	0.9900	5
3:42513748	acceptor_loss	0.9900

AlphaMissense

801 missense substitutions predicted likely pathogenic (of 2,997 scored), across 208 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D68	8	0.933	0.978
F182	8	0.933	0.985
H178	8	0.932	0.987
F350	8	0.924	0.959
F312	8	0.883	0.969
D196	8	0.874	0.940
F357	8	0.854	0.972
N175	8	0.835	0.984
C105	7	0.981	0.992
W73	7	0.975	0.998
C86	7	0.973	0.984
W110	7	0.973	0.998
C122	7	0.971	0.985
C72	7	0.968	0.983
C63	7	0.963	0.987
W67	7	0.961	0.996
E236	7	0.961	0.986
C285	7	0.946	0.973
W286	7	0.946	0.995
F185	7	0.942	0.979

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Prostate Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.29e-05
Bladder Urothelial Carcinoma (TCGA)	favorable	0.000159
Liver Hepatocellular Carcinoma (validation)	favorable	0.000431
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000626
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.000915

Disease associations

OMIM: gene MIM:192321 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST008103_49	Bipolar disorder	6e-7
GCST003134_7	Cerebrospinal fluid clusterin levels	3e-6
GCST012299_4	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	4e-6
GCST008156_19	Hip circumference adjusted for BMI	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524128 (PROTEIN FAMILY), CHEMBL5144 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 216 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1933349	MK-0893	2	216

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — VIP and PACAP receptors

Most potent curated ligand interactions (20 total), top 20:

Ligand	Action	Affinity	Parameter
[Ala11,22,28]VIP	Agonist	10.2	pEC50
VIP	Agonist	10.0	pEC50
[125I]VIP (human, mouse, rat)	Agonist	9.4	pKd
N-stearyl-[Nle17]VIP	Agonist	8.3	pIC50
[Lys15,Arg16,Leu27]VIP-(1-7)/GRF-(8-27)-NH2	Agonist	7.7	pIC50
PACAP-27	Agonist	7.6	pEC50
N-stearyl-[Nle17] neurotensin-(6-11)/VIP-(7-28)	Antagonist	7.5	pIC50
PACAP-38	Agonist	7.4	pEC50
[Arg16]chicken secretin	Agonist	7.2	pIC50
PG 97-269	Antagonist	7.1	pIC50
GHRH	Agonist	6.2	pKi
Ro 25-1553	Partial agonist	6.0	pEC50
PHI	Agonist	6.0	pIC50
helodermin	Agonist	6.0	pIC50
PHM	Agonist	5.7	pKi
PG 99-465	Agonist	5.5	pEC50
PHV	Agonist	5.5	pIC50
Ro 25-1392	Agonist	5.5	pKi
BAY 55-9837	Agonist	5.1	pIC50
secretin	Agonist	5.0	pKi

Binding affinities (BindingDB)

14 measured of 15 human assays (17 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5220770	EC50	0.03 nM
CHEMBL3884667	IC50	0.11 nM
CHEMBL219499	EC50	0.13 nM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	IC50	0.43 nM	US-10301272: Carboxamide or sulfonamide substituted thiazoles and related derivatives as modulators for the orphan nuclear receptor ROR[γ]
[Bip6]PACAP27	EC50	1 nM
NSC_0	KI	1.7 nM
PACAP	EC50	2.1 nM
CHEMBL1893324	EC50	2.3 nM
CHEMBL5219662	IC50	3.5 nM
PACAP27	EC50	5.6 nM
CHEMBL3736230	IC50	44.7 nM
CHEMBL3736134	IC50	57 nM
Ac-L-His-L-Ser-L-Asp-L-Ala-L-Val-L-Phe-L-Thr-L-Glu-L-Asn-L-Tyr-L-Thr-L-Lys-L-Leu-L-Arg-L-Lys-L-Gln-L-Nle-L-Ala-L-Ala-L-Lys-L-Lys(1)-L-Tyr-L-Leu-L-Asn-L-Asp(1)-L-Leu-L-Lys-L-Lys-Gly-Gly-L-Thr-NH2	KI	1020 nM
MK-0893	IC50	92000 nM

ChEMBL bioactivities

44 potent at pChembl≥5 of 45 total, top 43 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	EC50	0.02	nM	CHEMBL1893324
10.52	EC50	0.03	nM	CHEMBL5220770
10.40	IC50	0.04	nM	CHEMBL524658
10.30	IC50	0.05	nM	CHEMBL524658
10.21	Ki	0.062	nM	CHEMBL1893324
10.17	Ki	0.067	nM	CHEMBL1893324
9.96	IC50	0.11	nM	CHEMBL1893324
9.96	IC50	0.11	nM	CHEMBL3884667
9.92	IC50	0.12	nM	CHEMBL1893324
9.71	EC50	0.1952	nM	CHEMBL4294827
9.57	IC50	0.27	nM	CHEMBL1893324
9.45	EC50	0.3575	nM	CHEMBL4280734
9.33	IC50	0.47	nM	CHEMBL4128926
9.22	EC50	0.6	nM	CHEMBL219499
8.66	EC50	2.17	nM	CHEMBL4295255
8.35	EC50	4.426	nM	CHEMBL4281814
8.31	IC50	4.9	nM	CHEMBL4296687
8.25	EC50	5.658	nM	CHEMBL4277709
8.23	IC50	5.888	nM	CHEMBL524852
8.05	IC50	9	nM	CHEMBL3736134
8.04	EC50	9.088	nM	CHEMBL4294843
8.03	IC50	9.333	nM	CHEMBL3736134
8.02	EC50	9.515	nM	CHEMBL4291119
7.99	EC50	10.24	nM	CHEMBL4295255
7.94	IC50	11.48	nM	CHEMBL3736230
7.92	IC50	12	nM	CHEMBL3736230
7.92	IC50	12	nM	CHEMBL219499
7.85	IC50	14.13	nM	CHEMBL507480
7.19	EC50	64.4	nM	CHEMBL4284839
7.15	EC50	71.18	nM	CHEMBL4281905
7.05	EC50	89.34	nM	CHEMBL4282941
6.93	IC50	118.4	nM	CHEMBL5219662
6.88	EC50	133	nM	CHEMBL4282016
6.66	EC50	217.7	nM	CHEMBL4277441
6.53	EC50	293	nM	CHEMBL4286419
6.34	EC50	461.4	nM	CHEMBL4290756
6.29	EC50	516.3	nM	CHEMBL4277799
6.11	EC50	785.3	nM	CHEMBL4291903
6.04	EC50	912.1	nM	CHEMBL4277783
6.03	EC50	931.8	nM	CHEMBL4284961
5.85	EC50	1420	nM	CHEMBL4282364
5.85	EC50	1420	nM	CHEMBL4277870
5.82	EC50	1530	nM	CHEMBL4287451

PubChem BioAssay actives

22 with measured affinity, of 142 total; 12 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1915941: Agonist activity at VPAC1 in human SH-SY5Y cells assessed as cAMP accumulation incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay	ec50	<0.0001	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1915941: Agonist activity at VPAC1 in human SH-SY5Y cells assessed as cAMP accumulation incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay	ec50	<0.0001	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1336346: Displacement of [125I]PACAP1-27 from human recombinant PAC1 receptor expressed in CHO cells measured after 120 mins by scintillation counting method	ic50	<0.0001	uM
(3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1336366: Displacement of [125I]VIP from human recombinant VPAC1 receptor expressed in CHO cells measured after 60 mins by scintillation counting method	ic50	0.0001	uM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494772: Displacement of [125I]VIP from human recombinant VPAC1 receptor after 60 mins by scintillation counting analysis	ic50	0.0005	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]acetyl]amino]-3-methylpentanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoic acid	274568: Activity at human VPAC1 receptor in CHO cells by measuring cAMP accumulation	ec50	0.0006	uM
(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoic acid	340269: Inhibition of human VIP1 receptor	ic50	0.0049	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1261357: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC1 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0059	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-[4-[2-(4-fluorophenyl)ethynyl]phenyl]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1261357: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC1 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0090	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-[4-(2-phenylethynyl)phenyl]propan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1261357: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC1 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0115	uM
(3S)-4-[[2-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid	1261357: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC1 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0141	uM
(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-5-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-4-sulfanylbutanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]amino]hexanoic acid	1915944: Antagonist activity at VPAC1 in human SH-SY5Y cells assessed as inhibition of PACAP38-induced cAMP accumulation pre-incubated for 30 mins followed by agonist addition and measured after 75 mins by Eu-cAMP tracer based LANCE ultra cAMP assay	ic50	0.1184	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	7
Particulate Matter	increases expression, increases abundance, decreases reaction	4
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
chloroacetaldehyde	decreases expression	1
propionaldehyde	increases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
arsenite	increases methylation	1
afimoxifene	increases expression	1
sodium arsenite	decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-nonylphenol	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-tert-octylphenol	affects cotreatment, decreases expression	1
GW 4064	decreases reaction, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression, decreases reaction	1
Nebivolol	increases expression	1
Zoledronic Acid	increases expression	1
Cidofovir	increases expression	1
Alitretinoin	decreases reaction, increases expression	1
Glyphosate	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Chenodeoxycholic Acid	increases expression	1

ChEMBL screening assays

83 unique, capped per target: 71 binding, 12 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4880302	Binding	Vasoactive intestinal peptide receptor CEREP ligand profiling	Data for DCP probe ABT-546
CHEMBL2160607	Functional	Antagonist activity at human VPAC1 expressed in HT-29 cells assessed as inhibition of glucagon-induced cAMP accumulation preincubated for 30 mins prior to glucagon challenge measured after 30 mins post glucagon challenge by liquid scintilla	Discovery of a novel glucagon receptor antagonist N-[(4-{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes. — *J Med Chem*

Cellosaurus cell lines

9 cell lines: 4 spontaneously immortalized cell line, 3 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0TV	ACTOne VIPR1	Transformed cell line	Female
CVCL_H510	CHO-K1/VPAC1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV88	cAMP Hunter CHO-K1 VIPR1 Gs/Gq	Spontaneously immortalized cell line	Female
CVCL_KZ24	PathHunter CHO-K1 VIPR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB47	PathHunter U2OS VIPR1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_T424	Psi-CRIP-RxhVIPR-bsr	Transformed cell line	Male
CVCL_YK24	HEK293 VIPR1 HiTSeeker	Transformed cell line	Female
CVCL_YK65	U2OS VIPR1 cAMP-Nomad	Cancer cell line	Female
CVCL_ZK84	GeneBLAzer VPAC1-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for VIPR1 across ~30M SureChEMBL compounds — explore on Sugi Predict.