Target Information
| Target General Information | Top | |||||
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| Target ID |
T11011
(Former ID: TTDC00074)
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| Target Name |
Corticotropin-releasing factor receptor 2 (CRHR2)
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| Synonyms |
Corticotropin-releasinghormone receptor 2; CRHR2; CRH2 receptor; CRH-R 2; CRF2; CRF-R 2
Click to Show/Hide
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| Gene Name |
CRHR2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Heart failure [ICD-11: BD10-BD1Z] | |||||
| 2 | Binge eating disorder [ICD-11: 6B82] | |||||
| Function |
This is a receptor for corticotropin releasing factor. Shows high-affinity crf binding. Also binds to urocortin i, ii and iii. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
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| BioChemical Class |
GPCR secretin
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| UniProt ID | ||||||
| Sequence |
MDAALLHSLLEANCSLALAEELLLDGWGPPLDPEGPYSYCNTTLDQIGTCWPRSAAGALV
ERPCPEYFNGVKYNTTRNAYRECLENGTWASKINYSQCEPILDDKQRKYDLHYRIALVVN YLGHCVSVAALVAAFLLFLALRSIRCLRNVIHWNLITTFILRNVMWFLLQLVDHEVHESN EVWCRCITTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTERLRKCLFLFIGWCIPFPIIV AWAIGKLYYENEQCWFGKEPGDLVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTS ETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIMFIYFNSFLQSFQGFFVSVFYC FFNGEVRSAVRKRWHRWQDHHSLRVPMARAMSIPTSPTRISFHSIKQTAAV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T83F6G | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | RT-400 | Drug Info | Phase 2 | Acute decompensated heart failure | [2] | |
| 2 | Urocortin 2 | Drug Info | Phase 2 | Congestive heart failure | [3], [4] | |
| 3 | NBI-34041 | Drug Info | Phase 1 | Eating disorder | [5] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | PF-572778 | Drug Info | Terminated | Generalized anxiety disorder | [6] | |
| 2 | SC-241 | Drug Info | Terminated | Anxiety disorder | [7] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | RT-400 | Drug Info | [8] | |||
| Antagonist | [+] 3 Antagonist drugs | + | ||||
| 1 | Urocortin 2 | Drug Info | [1], [9], [10] | |||
| 2 | NBI-34041 | Drug Info | [5] | |||
| 3 | astressin | Drug Info | [13] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | PF-572778 | Drug Info | [11] | |||
| 2 | SC-241 | Drug Info | [12] | |||
| 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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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| cAMP signaling pathway | hsa04024 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| 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 | 3.58E-05 |
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| Closeness centrality | 1.72E-01 | Radiality | 1.27E+01 | Clustering coefficient | 7.00E-01 |
| Neighborhood connectivity | 7.00E+00 | Topological coefficient | 3.89E-01 | Eccentricity | 13 |
| 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 | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Cortocotropin releasing factor receptor signaling pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Class B/2 (Secretin family receptors) | |||||
| 2 | G alpha (s) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class B Secretin-like | |||||
| 2 | Corticotropin-releasing hormone | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Evolution of complementary peptide systems: teneurin C-terminal-associated peptides and corticotropin-releasing factor superfamilies. Ann N Y Acad Sci. 2009 Apr;1163:215-20. | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| 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: 927). | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013549) | |||||
| REF 5 | Emerging drugs for eating disorder treatment. Expert Opin Emerg Drugs. 2006 May;11(2):315-36. | |||||
| 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 800025528) | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008644) | |||||
| REF 8 | Advances in therapeutic peptides targeting G protein-coupled receptors. Nat Rev Drug Discov. 2020 Jun;19(6):389-413. | |||||
| REF 9 | Social isolation modulates corticotropin-releasing factor type 2 receptor, urocortin 1 and urocortin 2 mRNAs expression in the cardiovascular system of prairie voles. Peptides. 2009 May;30(5):940-6. | |||||
| REF 10 | Urocortin 2 protects against retinal degeneration following bilateral common carotid artery occlusion in the rat. Neurosci Lett. 2009 May 8;455(1):42-5. | |||||
| REF 11 | WO patent application no. 2013,1603,15, Genetic predictors of response to treatment with crhr1 antagonists. | |||||
| REF 12 | US patent application no. 2015,0094,310, Crhr1 antagonists for use in the treatment of patients having crh overactivity. | |||||
| REF 13 | Comparison of an agonist, urocortin, and an antagonist, astressin, as radioligands for characterization of corticotropin-releasing factor receptors. J Pharmacol Exp Ther. 1999 Feb;288(2):729-34. | |||||
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