Target Information
| Target General Information | Top | |||||
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| Target ID |
T86364
(Former ID: TTDC00204)
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| Target Name |
Vasoactive intestinal polypeptide receptor 1 (VIPR1)
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| Synonyms |
Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide receptor-1; Vasoactive intestinal peptide receptor 1; VPAC1; VPAC-1; VIPR1; VIP-R-1; Pituitary adenylate cyclase activating polypeptide type II receptor; PACAP-R-2; PACAP type II receptor
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| Gene Name |
VIPR1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Chronic obstructive pulmonary disease [ICD-11: CA22] | |||||
| 2 | Pulmonary hypertension [ICD-11: BB01] | |||||
| Function |
This is a receptor for vip. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The affinity is vip = pacap-27 > pacap-38.
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| BioChemical Class |
GPCR secretin
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| UniProt ID | ||||||
| Sequence |
MRPPSPLPARWLCVLAGALAWALGPAGGQAARLQEECDYVQMIEVQHKQCLEEAQLENET
IGCSKMWDNLTCWPATPRGQVVVLACPLIFKLFSSIQGRNVSRSCTDEGWTHLEPGPYPI ACGLDDKAASLDEQQTMFYGSVKTGYTIGYGLSLATLLVATAILSLFRKLHCTRNYIHMH LFISFILRAAAVFIKDLALFDSGESDQCSEGSVGCKAAMVFFQYCVMANFFWLLVEGLYL YTLLAVSFFSERKYFWGYILIGWGVPSTFTMVWTIARIHFEDYGCWDTINSSLWWIIKGP ILTSILVNFILFICIIRILLQKLRPPDIRKSDSSPYSRLARSTLLLIPLFGVHYIMFAFF PDNFKPEVKMVFELVVGSFQGFVVAILYCFLNGEVQAELRRKWRRWHLQGVLGWNPKYRH PSGGSNGATCSTQVSMLTRVSPGARRSSSFQAEVSLV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | Vasoactive intestinal peptide | Drug Info | Phase 2 | Pulmonary arterial hypertension | [2] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | Vasoactive intestinal peptide | Drug Info | [1], [3] | |||
| Agonist | [+] 2 Agonist drugs | + | ||||
| 1 | helodermin | Drug Info | [4] | |||
| 2 | PACAP-27 | Drug Info | [5] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Cholesterol | Ligand Info | |||||
| Structure Description | Cryo-EM structure of an activated VIP1 receptor-G protein complex | PDB:6VN7 | ||||
| Method | Electron microscopy | Resolution | 3.20 Å | Mutation | No | [6] |
| PDB Sequence |
ASLDEQQTMF
138 YGSVKTGYTI148 GYGLSLATLL158 VATAILSLFR168 KLHCTRNYIH178 MHLFISFILR 188 AAAVFIKDLA198 LFDSVGCKAA218 MVFFQYCVMA228 NFFWLLVEGL238 YLYTLLAVSF 248 FSERKYFWGY258 ILIGWGVPST268 FTMVWTIARI278 HFEDYGCWDT288 INSSLWWIIK 298 GPILTSILVN308 FILFICIIRI318 LLQKLRPPPY336 SRLARSTLLL346 IPLFGVHYIM 356 FAFFPDNFKP366 EVKMVFELVV376 GSFQGFVVAI386 LYCFLNGEVQ396 AELRRKWRRW 406 HLQ
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HIS180
3.361
ILE183
3.967
LEU187
3.704
SER212
4.162
VAL213
3.806
LYS216
4.445
ALA217
3.723
VAL220
4.369
PHE221
3.672
TYR224
3.572
PHE255
4.884
TRP256
4.608
ILE259
4.004
LEU260
3.939
TRP263
3.626
GLY264
3.811
SER267
3.386
PHE269
3.676
THR270
4.642
MET271
3.765
THR274
4.342
ILE278
3.616
TRP286
4.558
SER291
4.724
SER292
2.792
TRP295
3.362
ILE296
3.754
GLY299
4.880
PRO300
4.021
THR303
3.745
PHE309
4.989
PHE312
4.213
ILE313
3.759
ILE316
3.769
ARG317
3.822
LEU320
3.703
THR343
4.527
VAL352
4.951
ILE355
3.344
MET356
3.887
PHE359
4.007
PHE360
3.759
PRO361
3.739
PHE364
3.941
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 3.87E-04 |
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| Closeness centrality | 2.00E-01 | Radiality | 1.35E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.76E+01 | Topological coefficient | 2.05E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Glucocorticoid receptor regulatory network | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | G alpha (s) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | GPCRs, Class B Secretin-like | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19. | |||||
| REF 2 | ClinicalTrials.gov (NCT00464932) Vasoactive Intestinal Peptide in COPD. U.S. National Institutes of Health. | |||||
| REF 3 | Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69. | |||||
| REF 4 | Stable expression of the recombinant human VIP1 receptor in clonal Chinese hamster ovary cells: pharmacological, functional and molecular properties. Eur J Pharmacol. 1996 Apr 29;302(1-3):207-14. | |||||
| REF 5 | A systematic comparison of intracellular cyclic AMP and calcium signalling highlights complexities in human VPAC/PAC receptor pharmacology. Neuropharmacology. 2006 Nov;51(6):1086-98. | |||||
| REF 6 | Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy. Nat Commun. 2020 Aug 17;11(1):4121. | |||||
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