Target Information
| Target General Information | Top | |||||
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| Target ID |
T49072
(Former ID: TTDR00562)
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| Target Name |
Urotensin II receptor (UTS2R)
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| Synonyms |
Urotensin-II receptor GPR14; UTS2R; UR-II-R; G protein coupled receptor 14
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| Gene Name |
UTS2R
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Asthma [ICD-11: CA23] | |||||
| Function |
High affinity receptor for urotensin-2 and urotensin-2B. The activity of this receptor is mediated by a G-protein that activate a phosphatidylinositol-calcium second messenger system.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MALTPESPSSFPGLAATGSSVPEPPGGPNATLNSSWASPTEPSSLEDLVATGTIGTLLSA
MGVVGVVGNAYTLVVTCRSLRAVASMYVYVVNLALADLLYLLSIPFIVATYVTKEWHFGD VGCRVLFGLDFLTMHASIFTLTVMSSERYAAVLRPLDTVQRPKGYRKLLALGTWLLALLL TLPVMLAMRLVRRGPKSLCLPAWGPRAHRAYLTLLFATSIAGPGLLIGLLYARLARAYRR SQRASFKRARRPGARALRLVLGIVLLFWACFLPFWLWQLLAQYHQAPLAPRTARIVNYLT TCLTYGNSCANPFLYTLLTRNYRDHLRGRVRGPGSGGGRGPVPSLQPRARFQRCSGRSLS SCSPQPTDSLVLAPAAPARPAPEGPRAPA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | GSK1440115 | Drug Info | Phase 1 | Asthma | [2] | |
| 2 | SB-436811 | Drug Info | Phase 1 | Asthma | [2], [3] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | PALOSURAN | Drug Info | Discontinued in Phase 2 | Renal failure | [4], [5] | |
| 2 | SAR101099 | Drug Info | Discontinued in Phase 1 | Diabetic nephropathy | [6] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Antagonist | [+] 4 Antagonist drugs | + | ||||
| 1 | GSK1440115 | Drug Info | [7] | |||
| 2 | SAR101099 | Drug Info | [8] | |||
| 3 | S6716 | Drug Info | [13] | |||
| 4 | SB-611812 | Drug Info | [15] | |||
| Inhibitor | [+] 12 Inhibitor drugs | + | ||||
| 1 | SB-436811 | Drug Info | [1] | |||
| 2 | PALOSURAN | Drug Info | [1] | |||
| 3 | Ac-FWKY-NH2 | Drug Info | [1] | |||
| 4 | Ac-SFWKYS-NH2 | Drug Info | [1] | |||
| 5 | Ac-WKY-NH2 | Drug Info | [1] | |||
| 6 | Ac-[CFWKFC]-NH2 | Drug Info | [1] | |||
| 7 | Ac-[CFWkYC]-NH2 | Drug Info | [1] | |||
| 8 | AGTAD[CFWKYC]V | Drug Info | [1] | |||
| 9 | ICI-199441 | Drug Info | [11] | |||
| 10 | JNJ-28318706 | Drug Info | [12] | |||
| 11 | SB-328872 | Drug Info | [14] | |||
| 12 | SB-706375 | Drug Info | [1] | |||
| Agonist | [+] 3 Agonist drugs | + | ||||
| 1 | AC-7954 | Drug Info | [9] | |||
| 2 | FL104 | Drug Info | [10] | |||
| 3 | urotensin II-related peptide | Drug Info | [16] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| 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 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 Pathway Affiliation
Biological Network Descriptors
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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 | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.07E-04 | Radiality | 3.98E-03 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.00E+00 | Topological coefficient | . | Eccentricity | 1 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| 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 | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (q) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 2 | GPCR ligand binding | |||||
| 3 | GPCR downstream signaling | |||||
| 4 | GPCRs, Other | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Urotensin-II receptor modulators as potential drugs. J Med Chem. 2010 Apr 8;53(7):2695-708. | |||||
| REF 2 | ClinicalTrials.gov (NCT01424280) Single Dose Study of GSK1440115 in Patients With Asthma. U.S. National Institutes of Health. | |||||
| REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2164). | |||||
| REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3516). | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014355) | |||||
| REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033702) | |||||
| REF 7 | Effects of Urotensin II Receptor Antagonist, GSK1440115, in Asthma. Front Pharmacol. 2013; 4: 54. | |||||
| REF 8 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 365). | |||||
| REF 9 | Isochromanone-based urotensin-II receptor agonists. Bioorg Med Chem. 2005 Apr 15;13(8):3057-68. | |||||
| REF 10 | Novel and potent small-molecule urotensin II receptor agonists. Bioorg Med Chem. 2009 Jul 1;17(13):4657-65. | |||||
| REF 11 | Potent and selective small-molecule human urotensin-II antagonists with improved pharmacokinetic profiles. Bioorg Med Chem Lett. 2008 Jul 1;18(13):3716-9. | |||||
| REF 12 | Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits. J Med Chem. 2009 Dec 10;52(23):7432-45. | |||||
| REF 13 | Identification of nonpeptidic urotensin II receptor antagonists by virtual screening based on a pharmacophore model derived from structure-activity relationships and nuclear magnetic resonance studies on urotensin II. J Med Chem. 2002 Apr 25;45(9):1799-805. | |||||
| REF 14 | Urotensin-II receptor antagonists: synthesis and SAR of N-cyclic azaalkyl benzamides. Bioorg Med Chem Lett. 2008 Jul 15;18(14):3950-4. | |||||
| REF 15 | A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker. J Mol Cell Cardiol. 2005 Nov;39(5):785-91. | |||||
| REF 16 | Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain. Biochem Biophys Res Commun. 2003 Oct 24;310(3):860-8. | |||||
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