VIPR2

Summary

VIPR2 (vasoactive intestinal peptide receptor 2, HGNC:12695) is a protein-coding gene on chromosome 7q36.3, encoding Vasoactive intestinal polypeptide receptor 2 (P41587). 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.

Source: NCBI Gene 7434 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 68 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 26 tissues, sQTL in 5 (q < 0.05)
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.04 (unconstrained)
• MANE Select transcript: NM_003382
• Notable: 68 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12695
Approved symbol	VIPR2
Name	vasoactive intestinal peptide receptor 2
Location	7q36.3
Locus type	gene with protein product
Status	Approved
Aliases	VPAC2, VPAC2R
Ensembl gene	ENSG00000106018
Ensembl biotype	protein_coding
OMIM	601970
Entrez	7434

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 17 protein_coding, 13 nonsense_mediated_decay

MANE Select: ENST00000262178

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

ENST00000262178, ENST00000377633, ENST00000402066, ENST00000421760, ENST00000865374, ENST00000865375, ENST00000865376, ENST00000958129, ENST00000958130, ENST00000976294, ENST00001016842, ENST00001016843, ENST00001016844, ENST00001016845, ENST00001016846, ENST00001016847, ENST00001016848, ENST00001016849, ENST00001016850, ENST00001073518, ENST00001073519, ENST00001073520, ENST00001073521, ENST00001073522, ENST00001073523, ENST00001073524, ENST00001106178, ENST00001114212, ENST00001114213, ENST00001140918

RefSeq mRNA: 3 — MANE Select: NM_003382 NM_001304522, NM_001308259, NM_003382

CCDS: CCDS5950, CCDS78295

Canonical transcript exons

ENST00000262178 — 13 exons

Exon	Start	End
ENSE00000731012	159109812	159109919
ENSE00000731015	159103757	159103854
ENSE00000731018	159058481	159058578
ENSE00000731020	159043035	159043176
ENSE00000868045	159036752	159036902
ENSE00000868046	159035952	159036012
ENSE00000868047	159034581	159034650
ENSE00000868048	159034213	159034304
ENSE00000868049	159031938	159032067
ENSE00000868051	159028175	159030789
ENSE00001309515	159144721	159144867
ENSE00002510971	159031828	159031869
ENSE00003363471	159142446	159142545

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 89.68.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1431 / max 54.9618, expressed in 347 samples.

Highest expression (Bgee): mucosa of stomach, apex of heart, heart left ventricle, body of pancreas, cardiac ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

VIPR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 31 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	1.6e-46	-0.79	7:159114973:G:T
Artery Tibial	eqtl	4.0e-22	-0.29	7:159023884:A:C
Muscle Skeletal	eqtl	1.4e-19	+0.25	7:159145087:C:G
Brain Frontal Cortex BA9	eqtl	6.4e-16	-0.56	7:159155032:G:T
Nerve Tibial	eqtl	1.6e-15	-0.37	7:159303871:C:A
Brain Cortex	eqtl	7.0e-11	-0.54	7:159155032:G:T
Pancreas	sqtl	1.5e-09	+0.67	7:159113275:C:T
Artery Aorta	eqtl	1.7e-09	-0.30	7:159015725:C:T
Artery Tibial	sqtl	4.0e-07	+0.65	7:159073021:G:C
Esophagus Muscularis	eqtl	6.5e-07	-0.33	7:159295685:GCAA:G
Adipose Visceral Omentum	eqtl	1.1e-05	-0.19	7:159324309:T:C
Thyroid	eqtl	4.2e-05	+0.21	7:159028278:C:T
Heart Left Ventricle	eqtl	5.0e-05	+0.17	7:159159891:A:G
Breast Mammary Tissue	eqtl	3.4e-04	+0.22	7:159198677:C:T
Brain Cerebellar Hemisphere	eqtl	4.4e-04	-0.31	7:159145187:T:C
Brain Cerebellum	eqtl	6.0e-04	-0.37	7:159145187:T:C
Esophagus Gastroesophageal Junction	eqtl	6.8e-04	+0.19	7:159299252:G:C
Brain Anterior cingulate cortex BA24	eqtl	1.0e-03	-0.41	7:159153665:C:A
Pituitary	eqtl	2.5e-03	-0.17	7:159005931:G:C
Artery Aorta	sqtl	3.8e-03	+1.89	7:159092699:G:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
87127	0.6082	229
87130	0.2750	160
87129	0.1390	78
87128	0.1058	57
87126	0.0152	11

Top tissues by expression

showing 100 of 279 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	89.68	gold quality
apex of heart	UBERON:0002098	88.39	gold quality
heart left ventricle	UBERON:0002084	85.82	gold quality
body of pancreas	UBERON:0001150	85.81	gold quality
cardiac ventricle	UBERON:0002082	85.45	gold quality
endocervix	UBERON:0000458	84.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.10	gold quality
parotid gland	UBERON:0001831	83.59	gold quality
ascending aorta	UBERON:0001496	83.48	gold quality
thoracic aorta	UBERON:0001515	83.47	gold quality
aorta	UBERON:0000947	83.04	gold quality
popliteal artery	UBERON:0002250	82.83	gold quality
tibial artery	UBERON:0007610	82.83	gold quality
descending thoracic aorta	UBERON:0002345	82.62	gold quality
heart	UBERON:0000948	82.61	gold quality
left ovary	UBERON:0002119	82.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.20	gold quality
myocardium	UBERON:0002349	81.75	gold quality
right atrium auricular region	UBERON:0006631	81.65	gold quality
cardiac atrium	UBERON:0002081	81.17	gold quality
parietal pleura	UBERON:0002400	80.77	gold quality
right ovary	UBERON:0002118	79.82	gold quality
triceps brachii	UBERON:0001509	79.47	gold quality
omental fat pad	UBERON:0010414	79.28	gold quality
peritoneum	UBERON:0002358	79.26	gold quality
germinal epithelium of ovary	UBERON:0001304	79.25	silver quality
gluteal muscle	UBERON:0002000	79.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	78.98	gold quality
sigmoid colon	UBERON:0001159	78.91	gold quality
lower esophagus	UBERON:0013473	78.83	gold quality
adipose tissue of abdominal region	UBERON:0007808	78.47	gold quality
vagina	UBERON:0000996	77.98	gold quality
ovary	UBERON:0000992	77.01	gold quality
ectocervix	UBERON:0012249	76.70	gold quality
skeletal muscle tissue	UBERON:0001134	76.64	gold quality
seminal vesicle	UBERON:0000998	76.40	gold quality
vastus lateralis	UBERON:0001379	76.38	gold quality
corpus epididymis	UBERON:0004359	76.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.24	silver quality
superficial temporal artery	UBERON:0001614	76.10	gold quality
muscle tissue	UBERON:0002385	76.04	gold quality
lateral nuclear group of thalamus	UBERON:0002736	75.91	silver quality
left coronary artery	UBERON:0001626	75.88	gold quality
prostate gland	UBERON:0002367	75.87	gold quality
left ventricle myocardium	UBERON:0006566	75.77	gold quality
type B pancreatic cell	CL:0000169	75.68	gold quality
coronary artery	UBERON:0001621	75.66	gold quality
primary visual cortex	UBERON:0002436	75.62	gold quality
quadriceps femoris	UBERON:0001377	75.22	gold quality
tongue squamous epithelium	UBERON:0006919	75.16	gold quality
right coronary artery	UBERON:0001625	75.13	gold quality
body of uterus	UBERON:0009853	75.12	gold quality
olfactory bulb	UBERON:0002264	75.07	gold quality
uterine cervix	UBERON:0000002	74.98	gold quality
fundus of stomach	UBERON:0001160	74.97	gold quality
occipital lobe	UBERON:0002021	74.96	gold quality
muscle organ	UBERON:0001630	74.69	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.65	gold quality
smooth muscle tissue	UBERON:0001135	74.32	gold quality
muscle of leg	UBERON:0001383	74.21	gold quality
pleura	UBERON:0000977	74.18	gold quality
nasal cavity epithelium	UBERON:0005384	74.16	gold quality
oocyte	CL:0000023	74.14	gold quality
gastrocnemius	UBERON:0001388	73.95	gold quality
subthalamic nucleus	UBERON:0001906	73.89	gold quality
myometrium	UBERON:0001296	73.79	gold quality
dorsal plus ventral thalamus	UBERON:0001897	73.79	gold quality
substantia nigra pars reticulata	UBERON:0001966	73.74	gold quality
cardia of stomach	UBERON:0001162	73.72	silver quality
substantia nigra pars compacta	UBERON:0001965	73.68	gold quality
medial globus pallidus	UBERON:0002477	73.62	silver quality
vena cava	UBERON:0004087	73.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.30	gold quality
pancreas	UBERON:0001264	73.26	gold quality
ventral tegmental area	UBERON:0002691	73.16	gold quality
tendon of biceps brachii	UBERON:0008188	73.16	silver quality
body of stomach	UBERON:0001161	73.07	gold quality
body of tongue	UBERON:0011876	73.01	gold quality
endothelial cell	CL:0000115	72.87	silver quality
blood vessel layer	UBERON:0004797	72.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.55	gold quality
stomach	UBERON:0000945	72.54	gold quality
inferior vagus X ganglion	UBERON:0005363	72.52	gold quality
tongue	UBERON:0001723	72.43	gold quality
female reproductive system	UBERON:0000474	72.34	gold quality
cervix squamous epithelium	UBERON:0006922	72.34	gold quality
lateral globus pallidus	UBERON:0002476	72.29	gold quality
pons	UBERON:0000988	72.24	gold quality
nipple	UBERON:0002030	72.24	gold quality
mucosa of urinary bladder	UBERON:0001259	72.15	gold quality
biceps brachii	UBERON:0001507	72.11	gold quality
saphenous vein	UBERON:0007318	71.91	gold quality
secondary oocyte	CL:0000655	71.83	gold quality
pericardium	UBERON:0002407	71.75	gold quality
colon	UBERON:0001155	71.71	gold quality
urinary bladder	UBERON:0001255	71.68	gold quality
left uterine tube	UBERON:0001303	71.67	gold quality
diaphragm	UBERON:0001103	71.61	gold quality
trachea	UBERON:0003126	71.61	gold quality
large intestine	UBERON:0000059	71.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	144.02
E-ANND-3	yes	3.36

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Seminal vesicle	tissue	19.3	medium
Pons	tissue	15.6
Superior colliculi	tissue	14.4
Thalamus	tissue	14.3
Midbrain	tissue	13.6
Pancreas	tissue	13.5	not detected
Olfactory bulb	tissue	12.4
Heart muscle	tissue	11.6	medium
Epididymis	tissue	11.5	not detected
Vagina	tissue	11.0	medium
Spinal cord	tissue	9.0
Thymus	tissue	7.7
Putamen	tissue	7.4
Basal ganglia	tissue	7.0	not detected
Skeletal muscle	tissue	6.9	medium
Ovary	tissue	6.3	medium
Cervix	tissue	6.0	not detected
Retina	tissue	6.0
Placenta	tissue	5.4	high
Tongue	tissue	5.1
Postcentral gyrus	tissue	4.6
Choroid plexus	tissue	4.5
Hippocampus	tissue	4.4	not detected
Prostate	tissue	4.4	medium
Hypothalamus	tissue	4.1
Ventral forebrain	tissue	4.1
Smooth muscle	tissue	3.9	medium
Amygdala	tissue	3.7
Endometrium 1	tissue	3.6	medium
Hippocampal formation	tissue	3.2
Nucleus accumbens	tissue	2.9
Pituitary gland	tissue	2.7
Septum	tissue	2.7
Cerebral cortex	tissue	2.6	low
Temporal cortex	tissue	2.6
Gallbladder	tissue	2.4	not detected
Periaqueductal gray	tissue	2.3
Locus coeruleus	tissue	2.2
Somatosensory cortex	tissue	2.2
Urinary bladder	tissue	2.1	low
Retrosplenial and cingulate cortex	tissue	2.1
Motor cortex	tissue	2.0
Medulla oblongata	tissue	2.0
Entorhinal cortex	tissue	2.0
Retrosplenial cortex	tissue	2.0
Testis	tissue	1.9	medium
Substantia nigra	tissue	1.9
Small intestine	tissue	1.9	not detected
Stomach 1	tissue	1.8	not detected
Adipose tissue	tissue	1.7	high
Prefrontal cortex	tissue	1.6
Duodenum	tissue	1.6	not detected
Occipital cortex	tissue	1.6
Colon	tissue	1.4	low
Cerebellum	tissue	1.4	not detected
Esophagus	tissue	1.3	medium
Frontal cortex	tissue	1.3
Insular cortex	tissue	1.3
Fallopian tube	tissue	1.2	medium
Lymph node	tissue	1.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Temporo-occipital transitional zone (17.0), Blood vessel (13.4), Area striata (10.8), Transversal temporal gyrus, posterior (9.8), Parieto-insular cortex (9.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting VIPR2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 45 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4768-3P	98.16	66.02	2330

Functional genomics

gnomAD constraint: pLI 8.43e-13, LOEUF 1.04, missense Z 0.444 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000262178 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:159,030,619–159,036,842	306 / 285.8	1.07	no
7:159,036,843–159,036,885	4 / 16.5	0.24	yes (p 2.1e-03)
7:159,036,886–159,144,771	224 / 255.7	0.88	no

Literature-anchored findings (GeneRIF, showing 40)

• Detection of beta-galactosidase marker for human VPAC2/VIPR2 in cells withinin the suprachiasmatic nucleus (SCN) of transgenic mice indicates that VPAC2 may contribute to autoregulation and/or coupling within the SCN core and to control of the SCN shell. (PMID:15090046)
• analysis of a mutant form of VPAC2 shows its role in signaling and ligand binding (PMID:15302876)
• a novel recombinant agonist for VPAC2 is not active against PAC1 (PMID:16500728)
• The abnormal expression of VPCAP2-R mRNA in gallbladder tissue may play a role in the formation of gallbladder stones and gallbladder polyps (PMID:16552823)
• VPAC2-R mRNA was visualized only in the cerebellum of 7-22-year-old subjects. (PMID:16572459)
• splice variants may modify the immunoregulatory contributions of the VIP-VPAC2 axis (PMID:16888203)
• identification and characterization of novel five-transmembrane(5TM) isoforms of VPAC2 (PMID:16934434)
• altered expression of VPAC2 in activated CD4+ T cells derived from multiple sclerosis (MS) patients rendered CD4+ T cells less responsive to VIP and skewed the system to a predominantly T(h)1 direction. (PMID:17077178)
• Daily stimulation of VPAC2, but not VPAC1 or PAC1, resulted in up to 90% inhibition of X4 or R5 productive infections in either cell lines or PBMCs. (PMID:17257640)
• analysis of VIP 16gamma-glutamyl diamino derivative positive charges on hVPAC1 and hVPAC2 receptor function (PMID:17883247)
• VIP(Vasoactive intestinal peptide) expression was decreased in Rhematoid Arthritis (RA) synovial fibroblasts (FLS) compared with Osteoarthritis(OA) FLS;in RA FLS, VPAC2 (VIP receptor type 2) mediates the antiinflammatory effects of VIP (PMID:18383383)
• a novel mechanism of calmodulin in regulating PACAP signaling by possible interaction with the inactive state of PAC1 and VPAC2 receptors. (PMID:19269029)
• 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)
• VPAC2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans. (PMID:20395540)
• VPAC(2) receptor presents an extranuclear localization and its protein expression is lower than that of VPAC(1) receptor in human breast tissue samples (PMID:20691743)
• increased expression in patients with allergic rhinitis (PMID:21711977)
• gene expression level and cAMP signaling of VIPR2 were increased in patients carrying 7q36.3 microduplications, thus implicating VIPR2 in the etiology of schizophrenia.[review] (PMID:21721910)
• mRNA expression of the VPAC1 receptor was detected in 51% of the tumor specimens, while the incidence of mRNA expression for VPAC2 was 46%. (PMID:21769421)
• The overexpression of VPAC1 and VPAC2 receptors and COX-2 in cancer tissue gives them a potential role as targets for diagnosis of prostate cancer. (PMID:22763881)
• PACAP causes PAC1/VPAC2 receptor mediated hypertension and sympathoexcitation in normal and hypertensive rats. (PMID:22886412)
• Conclude that VPAC2/PAC1 receptors require NO in series to effect cutaneous active vasodilation during heat stress in humans. (PMID:22961270)
• Genetic testing for VIPR2-LCR-associated inversions should be performed on available cohorts of psychiatric patients to evaluate their potential pathogenic role (PMID:23073313)
• This is the first study to suggest a role of VIPR2 in the genetic susceptibility to high myopia. EGR1, JUN, FOS and VIP are unlikely to be important in predisposing humans to high myopia. (PMID:23637909)
• Data indicate that VIP and PACAP increased macrophage resistance to HIV-1 replication by inducing the synthesis of beta-chemokines CCL3 and CCL5 and IL-10 following preferential activation of the receptors VPAC2 and PAC1. (PMID:23818986)
• CD4+ T cells in HIV infection show increased levels of expression of VPAC2 (PMID:24469917)
• This study suggest that carriers of microduplication genotypes of VIPR2 are predisposed to SCZ in Han Chinese. (PMID:24794882)
• Monocytes from Sjogren’s syndrome patients display increased vasoactive intestinal peptide receptor 2 expression and impaired apoptotic cell phagocytosis. (PMID:24827637)
• Lower CpG methylation of VIPR2 in the saliva of children with ADHD. (PMID:26304033)
• The results reveal that more severe inflammation, based on high levels of IL-6, is associated with lower expression of VPAC1 and, conversely, with increased expression of VPAC2. (PMID:26881970)
• The ‘CC’ genotype of the VIPR2 gene was nominally associated with an increased risk of SCZ in male Han Chinese patients. (PMID:27156032)
• In vitro-polarized macrophages by GM-CSF (GM-MO), with a proinflammatory profile, expressed higher levels of VIP receptors, vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2, respectively), than macrophages polarized by M-CSF (M-MO) with anti-inflammatory activities. RA synovial macrophages, according to their GM-CSF-like polarization state, expressed both VPAC1 and VPAC2. (PMID:27381006)
• a novel gene duplication syndrome (10q21.2q21.3 microduplication) and new evidence for VIPR2 duplication, as a candidate gene for autism, are reported. (PMID:27796743)
• Data suggest that VIPR2, which is a negative regulator of smooth muscle cell proliferation, might be a novel tumor suppressor gene in uterine leiomyosarcomas. (PMID:29063609)
• Activation of Th lymphocytes alters pattern expression and cellular location of VIP receptors in healthy donors and early arthritis patients. (PMID:31089161)
• Predictive Genes for the Prognosis of Central Serous Chorioretinopathy. (PMID:31331787)
• Study reports for a first time an association of a (3’ UTR) variant rs885863 in VIPR2 gene and opioid addiction. This single nucleotide polymorphism is an expression quantitative trait locus for VIPR2 and a long intergenic non-coding RNA, lincRNA 689. The study provides preliminary insight into the relationship between genetic variants in circadian rhythm genes and lincRNA in their vicinity, and opioid addiction. (PMID:31689297)
• The myopia susceptibility locus vasoactive intestinal peptide receptor 2 (VIPR2) contains variants with opposite effects. (PMID:31796800)
• Association of VIPR2 and ZMAT4 with high myopia. (PMID:32166996)
• Dysfunction of VIPR2 leads to myopia in humans and mice. (PMID:33318135)
• Identification of rare mutations of the vasoactive intestinal peptide receptor 2 gene in schizophrenia. (PMID:35353798)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vipr2	ENSDARG00000012353
mus_musculus	Vipr2	ENSMUSG00000011171
rattus_norvegicus	Vipr2	ENSRNOG00000004317

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), VIPR1 (ENSG00000114812), 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:107166) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 21 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal circadian behavior persistence	2
arrhythmic circadian behavior persistence	2
seminiferous tubule degeneration	1
decreased body length	1
decreased body weight	1
decreased locomotor activity	1
reduced male fertility	1
decreased IgE level	1
increased insulin sensitivity	1
abnormal cytokine secretion	1
increased lean body mass	1
increased circulating triiodothyronine level	1
decreased susceptibility to type I hypersensitivity reaction	1
increased susceptibility to type IV hypersensitivity reaction	1
increased interferon-gamma secretion	1
increased interleukin-2 secretion	1
decreased interleukin-4 secretion	1
decreased total body fat amount	1
decreased food intake	1
abnormal circadian behavior	1
abnormal circardian behavior entrainment	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
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

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
LINC00689	ncRNA	154822
DYNC2I1	protein-coding	55112

Protein

Protein identifiers

Vasoactive intestinal polypeptide receptor 2 — P41587 (reviewed: P41587)

Alternative names: Helodermin-preferring VIP receptor, Pituitary adenylate cyclase-activating polypeptide type III receptor, VPAC2 receptor

All UniProt accessions (4): P41587, C9JCP7, E9PCR5, X5D7Q6

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 potency PACAP38 = VIP > PACAP27. 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. May be coupled to phospholipase C.

Subunit / interactions. Interacts with ADCYAP1/PACAP (via N-terminal extracellular domain); activated by PACAP27 and CAPAC38 neuropeptides. Interacts with VIP; the interaction results in VIPR1 activation.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in CD4+ T-cells, but not in CD8+ T-cells. Expressed in the T-cell lines Jurkat, Peer, MOLT-4, HSB, YT and SUP-T1, but not in the T-cell lines HARRIS and HuT 78.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P41587-1	1	yes
P41587-2	2

RefSeq proteins (3): NP_001291451, NP_001295188, NP_003373* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000832	GPCR_2_secretin-like	Family
IPR001571	GPCR_2_VIP_rcpt	Family
IPR001879	GPCR_2_extracellular_dom	Domain
IPR002284	GPCR_2_VIP_rcpt_2	Family
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR047035	VIP-R2_7TM	Domain
IPR050332

Pfam: PF00002, PF02793

UniProt features (61 total): helix 20, topological domain 8, transmembrane region 7, mutagenesis site 5, strand 5, disulfide bond 4, glycosylation site 3, splice variant 2, sequence variant 2, turn 2, signal peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
2X57	Crystal structure of the extracellular domain of human Vasoactive intestinal polypeptide …	X-RAY DIFFRACTION	2.1
7VQX	Cryo-EM structure of human vasoactive intestinal polypeptide receptor 2 (VIP2R) in …	ELECTRON MICROSCOPY	2.74
7WBJ	Cryo-EM structure of N-terminal modified human vasoactive intestinal polypeptide receptor …	ELECTRON MICROSCOPY	3.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41587-F1	74.63	0.26

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 7VQX, 7WBJ

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): focal adhesion sites

Antibody reliability (HPA): IH approved · IF 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 (4)

Type	Positions
Disulfide bond	38–61, 52–93, 75–109, 202–271

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	58, 88, 92

Mutagenesis-validated functional residues (5)

Position	Phenotype
79	decreased adcyap1/pacap27 potency for vipr2.
123	decreased adcyap1/pacap27 potency for vipr2.
184	decreased adcyap1/pacap27 potency for vipr2.
209	increased adcyap1/pacap27 potency for vipr2.
357	decreased adcyap1/pacap27 potency for vipr2.

Function

Pathways and Gene Ontology

Reactome pathways

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

7 pathways:

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

MSigDB gene sets: 112 (showing top): REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, MODULE_99, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, AACTTT_UNKNOWN, MORF_WNT1, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, YAGI_AML_WITH_11Q23_REARRANGED, RAAGNYNNCTTY_UNKNOWN, GRYDER_PAX3FOXO1_TOP_ENHANCERS

GO Biological Process (6): signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), cell-cell signaling (GO:0007267), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (7): pituitary adenylate cyclase-activating polypeptide receptor activity (GO:0001634), G protein-coupled receptor activity (GO:0004930), 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), protein binding (GO:0005515)

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

19 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
adenylate cyclase-activating G protein-coupled receptor signaling pathway	BP	direct assay
plasma membrane	CC	direct assay
pituitary adenylate cyclase-activating polypeptide receptor activity	MF	mutant phenotype
vasoactive intestinal polypeptide receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,080 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VIPR2	VIP	P01282	959
VIPR2	ADCYAP1	P18509	926
VIPR2	PPIP5K2	O43314	844
VIPR2	SCT	P09683	754
VIPR2	PER2	O15055	754
VIPR2	CRY1	Q16526	727
VIPR2	PROK2	Q9HC23	599
VIPR2	GCG	P01275	571
VIPR2	GHRH	P01286	539
VIPR2	DYNC2I1	Q8WVS4	534
VIPR2	GRP	P07491	523
VIPR2	NMS	Q5H8A3	502
VIPR2	CHODL	Q9H9P2	483
VIPR2	ESYT2	A0FGR8	478
VIPR2	BMAL1	O00327	470

IntAct

Human interaction partners of VIPR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
RAMP3	physical association	0.400	4
RAMP1	physical association	0.400	2
RAMP2	physical association	0.400	2
DBNDD2	physical association	0.370	1
RGS14	physical association	0.370	1
URM1	physical association	0.370	1
C15orf61	association	0.350	1
EI24	association	0.350	1
RABGAP1L	association	0.350	1
SLC33A1	association	0.350	1

BioGRID (272 interactions; top human partners by supporting records): ADCK1 (Affinity Capture-MS; 2 records), ADCK4 (Affinity Capture-MS; 2 records), AGPAT4 (Affinity Capture-MS; 2 records), ALG10 (Affinity Capture-MS; 2 records), ATP5A1 (Affinity Capture-MS; 2 records), ATP5B (Affinity Capture-MS; 2 records), BRAT1 (Affinity Capture-MS; 2 records), BTAF1 (Affinity Capture-MS; 2 records), BZW2 (Affinity Capture-MS; 2 records), C10orf35 (Affinity Capture-MS; 2 records), C1orf112 (Affinity Capture-MS; 2 records), C4orf32 (Affinity Capture-MS; 2 records), CDS1 (Affinity Capture-MS; 2 records), CERS2 (Affinity Capture-MS; 2 records), CERS5 (Affinity Capture-MS; 2 records)

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-VIPR2 complex	2	SCTR, VIPR2
★ RAMP1-VIPR2 complex	2	RAMP1, VIPR2
★ RAMP2-VIPR2 complex	2	RAMP2, VIPR2
★ RAMP3-VIPR2 complex	2	RAMP3, VIPR2

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 VIPR2: 68 ClinVar records (0 pathogenic / likely pathogenic); 12 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	5
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 1,882):

Position(s)	Effect	Δscore	Sites
7:159031870–159031871	acceptor_loss	1.0000	4
7:159036750–159036751	donor_loss	1.0000	3
7:159036903–159036904	acceptor_loss	1.0000	6
7:159036911	acceptor_gain	1.0000
7:159103755–159103756	donor_loss	1.0000	5
7:159142546	acceptor_loss	1.0000
7:159142556	acceptor_gain	1.0000
7:159031826–159031827	donor_loss	0.9900	5
7:159031870	acceptor_loss	0.9900	2
7:159031970	donor_gain	0.9900

AlphaMissense

959 missense substitutions predicted likely pathogenic (of 2,849 scored), across 247 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
H162	8	0.967	0.995
F166	8	0.962	0.994
D180	8	0.949	0.986
F337	8	0.933	0.962
F299	8	0.929	0.985
F169	8	0.919	0.990
N379	8	0.901	0.989
D57	8	0.895	0.974
F344	8	0.891	0.983
N159	8	0.887	0.991
F366	8	0.824	0.957
D273	8	0.798	0.941
C93	7	0.996	0.999
C75	7	0.994	0.997
C61	7	0.993	0.997
W98	7	0.992	1.000
C109	7	0.991	0.995
W62	7	0.990	0.999
C271	7	0.990	0.996
W272	7	0.990	0.999

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	4.77e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	7.12e-05

Disease associations

OMIM: gene MIM:601970 | disease phenotypes:

GWAS associations

12 associations:

Study	Trait	p-value
GCST010002_269	Refractive error	2e-37
GCST001881_4	Myopia (pathological)	9e-14
GCST012490_241	Femur bone mineral density x serum urate levels interaction	9e-12
GCST006291_50	Spherical equivalent or myopia (age of diagnosis)	5e-10
GCST006291_76	Spherical equivalent or myopia (age of diagnosis)	5e-8
GCST006068_2	Sub-foveal choroidal thickness	7e-8
GCST010257_1	Diastolic blood pressure x quantitative lifestyle risk score interaction (1df test)	1e-7
GCST010256_1	Diastolic blood pressure x quantitative lifestyle risk score interaction (2df test)	3e-7
GCST011920_2	Hearing loss in noise exposure	2e-6
GCST007159_25	Corneal astigmatism	3e-6
GCST010397_49	Gut microbiota (bacterial taxa, rank normal transformation method)	3e-6
GCST011358_8	Academic attainment (English)	8e-6

EFO canonical traits (from GWAS)

9 canonical traits:

EFO ID	Trait name
EFO:0004207	pathological myopia
EFO:0009281	choroidal thickness measurement
EFO:0004847	age at onset
EFO:1002040	Corneal astigmatism
EFO:0006336	diastolic blood pressure
EFO:0010724	lifestyle measurement
EFO:0007874	gut microbiome measurement
EFO:0011015	educational attainment
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4524128 (PROTEIN FAMILY), CHEMBL4532 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 867 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1981592	AVIPTADIL	3	651
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 (19 total), top 19:

Ligand	Action	Affinity	Parameter
[125I]VIP (human, mouse, rat)	Agonist	9.2	pKd
[125I]BAY 55-9837	Agonist	9.2	pKd
N-stearyl-[Nle17]VIP	Agonist	9.0	pIC50
helodermin	Agonist	8.5	pIC50
Ro 25-1553	Agonist	8.3	pEC50
PHV	Agonist	8.0	pIC50
Ro 25-1392	Agonist	8.0	pKi
PACAP-38	Agonist	7.7	pEC50
PACAP-27	Agonist	7.6	pEC50
PG 99-465	Partial agonist	7.6	pIC50
PHI	Agonist	7.5	pIC50
VIP	Agonist	7.3	pEC50
N-stearyl-[Nle17] neurotensin-(6-11)/VIP-(7-28)	Antagonist	7.3	pIC50
BAY 55-9837	Agonist	7.2	pIC50
PG 97-269	Antagonist	5.5	pIC50
secretin	Agonist	5.3	pIC50
[Arg16]chicken secretin	Agonist	5.3	pIC50
[Ala11,22,28]VIP	Agonist	5.0	pEC50
[Lys15,Arg16,Leu27]VIP-(1-7)/GRF-(8-27)-NH2	Agonist	4.5	pIC50

Binding affinities (BindingDB)

32 measured of 32 human assays (57 total across all organisms); most potent 32 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5220770	EC50	0.03 nM
CHEMBL3102930	EC50	0.05 nM
CHEMBL3102924	EC50	0.1 nM
CHEMBL3102925	EC50	0.11 nM
CHEMBL219499	EC50	0.13 nM
CHEMBL3102919	EC50	0.14 nM
CHEMBL1981592	EC50	0.19 nM
CHEMBL3102922	EC50	0.21 nM
CHEMBL3102929	EC50	0.21 nM
CHEMBL3102931	EC50	0.33 nM
CHEMBL3102921	EC50	0.38 nM
CHEMBL3105020	EC50	0.39 nM
Ac-HSDAVFTDQYTRLRKQVAAKKYLQSIKQKRYC	EC50	0.6 nM
[Bip6]PACAP27	EC50	1 nM
CHEMBL3102923	EC50	1.2 nM
CHEMBL3102926	EC50	1.4 nM
CHEMBL3105019	EC50	1.5 nM
CHEMBL3102927	EC50	1.5 nM
NSC_0	KI	1.7 nM
CHEMBL1893324	EC50	2.3 nM
CAS_150828-75-4	KI	3.4 nM
CHEMBL5219662	IC50	3.5 nM
CHEMBL3102928	EC50	3.8 nM
PACAP27	EC50	5.6 nM
CHEMBL3102920	EC50	6.6 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
CHEMBL2159349	IC50	1340 nM
CHEMBL2159347	IC50	1840 nM
CHEMBL2159348	IC50	2420 nM
MK-0893	IC50	92000 nM

ChEMBL bioactivities

81 potent at pChembl≥5 of 86 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.31	EC50	0.049	nM	CHEMBL3102930
10.22	EC50	0.06	nM	CHEMBL5220770
10.11	EC50	0.07845	nM	CHEMBL4294827
10.10	EC50	0.08	nM	CHEMBL1893324
10.06	EC50	0.087	nM	CHEMBL219499
10.00	EC50	0.1	nM	CHEMBL3102924
9.96	EC50	0.11	nM	CHEMBL3102925
9.85	EC50	0.14	nM	CHEMBL3102919
9.74	EC50	0.1804	nM	CHEMBL4277441
9.72	EC50	0.19	nM	AVIPTADIL
9.68	EC50	0.21	nM	CHEMBL3102929
9.68	EC50	0.21	nM	CHEMBL3102922
9.48	EC50	0.33	nM	CHEMBL3102931
9.42	EC50	0.38	nM	CHEMBL3102921
9.41	EC50	0.39	nM	CHEMBL3105020
9.38	EC50	0.422	nM	CHEMBL4291119
9.28	EC50	0.5286	nM	CHEMBL4277799
9.23	EC50	0.5928	nM	CHEMBL4285873
9.22	EC50	0.6	nM	CHEMBL440082
9.19	EC50	0.646	nM	CHEMBL4282016
9.09	EC50	0.8162	nM	CHEMBL4281547
9.07	EC50	0.8586	nM	CHEMBL4277870
9.02	EC50	0.9629	nM	CHEMBL4294951
8.99	EC50	1.018	nM	CHEMBL4289726
8.94	EC50	1.16	nM	CHEMBL3102923
8.93	EC50	1.166	nM	CHEMBL4291903
8.90	EC50	1.266	nM	CHEMBL4286419
8.90	EC50	1.258	nM	CHEMBL4276843
8.88	EC50	1.334	nM	CHEMBL4282364
8.86	EC50	1.37	nM	CHEMBL3102926
8.86	EC50	1.372	nM	CHEMBL4283432
8.83	EC50	1.49	nM	CHEMBL3102927
8.82	EC50	1.52	nM	CHEMBL3105019
8.46	EC50	3.472	nM	CHEMBL4284858
8.45	EC50	3.515	nM	CHEMBL4287451
8.42	EC50	3.8	nM	CHEMBL3102928
8.35	IC50	4.5	nM	CHEMBL5219662
8.25	EC50	5.579	nM	CHEMBL4278228
8.18	EC50	6.6	nM	CHEMBL3102920
7.99	IC50	10.23	nM	CHEMBL524852
7.89	IC50	13	nM	CHEMBL219499
7.64	IC50	22.91	nM	CHEMBL507480
7.57	IC50	27	nM	CHEMBL440082
7.44	IC50	36.31	nM	CHEMBL3736134
7.44	IC50	36	nM	CHEMBL3736134
7.30	EC50	50.25	nM	CHEMBL4281905
7.28	IC50	53	nM	CHEMBL3736230
7.27	IC50	53.7	nM	CHEMBL3736230
7.10	EC50	79.64	nM	CHEMBL4280734
7.02	EC50	95.59	nM	CHEMBL4284961

PubChem BioAssay actives

32 with measured affinity, of 61 total; 28 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
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,16Z,22S)-22-[[(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-5-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]-5-(4-aminobutyl)-8-(3-amino-3-oxopropyl)-2-(3-carbamimidamidopropyl)-11,22-dimethyl-3,6,9,23-tetraoxo-1,4,7,10-tetrazacyclotricos-16-ene-11-carbonyl]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-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	<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-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	1915942: Agonist activity at VPAC2 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
(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	274566: Activity at human VPAC2 receptor in CHO cells by measuring cAMP accumulation	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	1915942: Agonist activity at VPAC2 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
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,20S)-20-[[(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-5-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]-8-(4-aminobutyl)-2-methyl-3,6,9,17,21-pentaoxo-5-propan-2-yl-1,4,7,10,16-pentazacyclohenicosane-11-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0001	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,5S,8S,11S,20S)-20-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-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-5-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]-3-methylpentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-8-(2-amino-2-oxoethyl)-2-[(4-hydroxyphenyl)methyl]-5-(2-methylpropyl)-3,6,9,17,21-pentaoxo-1,4,7,10,16-pentazacyclohenicosane-11-carbonyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0001	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-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-5-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]-3-methylpentanoyl]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-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0001	uM
(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-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-5-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	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0002	uM
(2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-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-5-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]-3-methylpentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-2-methylhept-6-enoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-2-methylhept-6-enoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0002	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-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-5-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]-3-methylpentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0002	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,16Z,22S)-22-[[(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-5-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]-8-(4-aminobutyl)-2,11,22-trimethyl-3,6,9,23-tetraoxo-5-propan-2-yl-1,4,7,10-tetrazacyclotricos-16-ene-11-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0003	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-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-5-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-carboxybutanoyl]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-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0004	uM
(2S)-6-amino-2-[[2-[[(2S,5S,8S,11S,16Z,22S)-22-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-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-5-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]-3-methylpentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-5-[(2S)-butan-2-yl]-2-(hydroxymethyl)-11,22-dimethyl-8-(2-methylpropyl)-3,6,9,23-tetraoxo-1,4,7,10-tetrazacyclotricos-16-ene-11-carbonyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0004	uM
(3S)-3-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-5-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)-5-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-6-amino-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-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]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-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]-1,5-dioxopentan-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]-4-oxobutanoic acid	274566: Activity at human VPAC2 receptor in CHO cells by measuring cAMP accumulation	ec50	0.0006	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,20S)-20-[[(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-5-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]-5-(4-aminobutyl)-8-(3-amino-3-oxopropyl)-2-(3-carbamimidamidopropyl)-3,6,9,17,21-pentaoxo-1,4,7,10,16-pentazacyclohenicosane-11-carbonyl]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-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0012	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-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-5-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]-2-methylhept-6-enoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]-2-methylhept-6-enoyl]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-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0014	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-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-5-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]-2-methylhept-6-enoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-2-methylhept-6-enoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0015	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,5S,8S,11S,16Z,22S)-22-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-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-5-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]-3-methylpentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-8-(2-amino-2-oxoethyl)-2-[(4-hydroxyphenyl)methyl]-11,22-dimethyl-5-(2-methylpropyl)-3,6,9,23-tetraoxo-1,4,7,10-tetrazacyclotricos-16-ene-11-carbonyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0015	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-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-5-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]-3-methylpentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-2-methylhept-6-enoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-2-methylhept-6-enoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0038	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	1915945: Antagonist activity at VPAC2 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	0.0045	uM
(2S)-6-amino-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-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-5-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-carboxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]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-oxobutanoyl]amino]acetyl]amino]hexanoic acid	1062174: Agonist activity at human VPAC2 expressed in CHO Flp-in cells assessed as accumulation of cAMP after 30 mins by TR-FRET assay	ec50	0.0066	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	1261358: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC2 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0102	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	1261358: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC2 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0229	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	1261358: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC2 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0360	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	1261358: Displacement of Ac-[125I]-PACAP27 from recombinant human VPAC2 expressed in CHO cells after 90 mins by gamma counting analysis	ic50	0.0530	uM
3-[[4-[(1S)-1-[3-(3,4-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)pyrazol-1-yl]ethyl]benzoyl]amino]propanoic acid	693739: Antagonist activity at human VPAC2 expressed in CHO 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 scintillation counter	ic50	1.7000	uM
3-[[4-[(1S)-1-[3-(2,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)pyrazol-1-yl]ethyl]benzoyl]amino]propanoic acid	693739: Antagonist activity at human VPAC2 expressed in CHO 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 scintillation counter	ic50	2.6000	uM
3-[[4-[(1S)-1-[3-[3-chloro-5-(trifluoromethyl)phenyl]-5-(6-methoxynaphthalen-2-yl)pyrazol-1-yl]ethyl]benzoyl]amino]propanoic acid	693739: Antagonist activity at human VPAC2 expressed in CHO 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 scintillation counter	ic50	2.6000	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Valproic Acid	affects expression, decreases methylation	2
Aflatoxin B1	increases methylation, decreases methylation	2
sulforaphane	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
Olanzapine	affects expression	1
Amisulpride	decreases expression	1
Acetaminophen	decreases expression	1
Cyclic AMP	affects binding, increases abundance	1
Ethanol	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	affects expression	1
Estradiol	decreases expression	1
Folic Acid	affects cotreatment, increases expression	1
Haloperidol	decreases expression	1
Methapyrilene	increases methylation	1
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression	1
Tunicamycin	increases expression	1
Zinc	affects cotreatment, affects expression	1
Thapsigargin	increases expression	1

ChEMBL screening assays

27 unique, capped per target: 14 functional, 13 binding

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
CHEMBL2160805	Functional	Antagonist activity at human VPAC2 expressed in CHO 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 scintillati	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

11 cell lines: 6 spontaneously immortalized cell line, 3 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C0TW	ACTOne VIPR2	Transformed cell line	Female
CVCL_E0SX	Ubigene HeLa VIPR2 KO	Cancer cell line	Female
CVCL_E4PY	KOLF2.1J VIPR2 72.1kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_H492	CHO-K1/PAC1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_H511	CHO-K1/VPAC2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KA21	CHO-K1/CRE-Luc/VPAC2	Spontaneously immortalized cell line	Female
CVCL_KV89	cAMP Hunter CHO-K1 VIPR2 Gs	Spontaneously immortalized cell line	Female
CVCL_KZ25	PathHunter CHO-K1 VIPR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LB48	PathHunter U2OS VIPR2 Total GPCR Internalization	Cancer cell line	Female
CVCL_YK66	U2OS VIPR2 cAMP-Nomad	Cancer cell line	Female

Clinical trials (associated diseases)

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

5 trials:

NCT	Phase	Status	Title
NCT03600649	Phase 1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	Phase 1/2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	Phase 1/2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	Phase 1/2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for VIPR2 across ~30M SureChEMBL compounds — explore on Sugi Predict.