Target Information
| Target General Information | Top | |||||
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| Target ID |
T58589
(Former ID: TTDR00405)
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| Target Name |
B1 bradykinin receptor (BDKRB1)
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| Synonyms |
BRADYB1; BK-1 receptor; B1R
Click to Show/Hide
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| Gene Name |
BDKRB1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Retinopathy [ICD-11: 9B71] | |||||
| 2 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| 3 | Osteoarthritis [ICD-11: FA00-FA05] | |||||
| Function |
This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MASSWPPLELQSSNQSQLFPQNATACDNAPEAWDLLHRVLPTFIISICFFGLLGNLFVLL
VFLLPRRQLNVAEIYLANLAASDLVFVLGLPFWAENIWNQFNWPFGALLCRVINGVIKAN LFISIFLVVAISQDRYRVLVHPMASRRQQRRRQARVTCVLIWVVGGLLSIPTFLLRSIQA VPDLNITACILLLPHEAWHFARIVELNILGFLLPLAAIVFFNYHILASLRTREEVSRTRC GGRKDSKTTALILTLVVAFLVCWAPYHFFAFLEFLFQVQAVRGCFWEDFIDLGLQLANFF AFTNSSLNPVIYVFVGRLFRTKVWELYKQCTPKSLAPISSSHRKEIFQLFWRN Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T00W4R | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | Safotibant | Drug Info | Phase 2 | Diabetic macular edema | [2] | |
| 2 | SSR-240612 | Drug Info | Phase 2 | Rheumatoid arthritis | [3], [4] | |
| 3 | BI 113823 | Drug Info | Phase 1 | Osteoarthritis | [5] | |
| Mode of Action | [+] 3 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Safotibant | Drug Info | [6] | |||
| 2 | BI 113823 | Drug Info | [8] | |||
| Antagonist | [+] 4 Antagonist drugs | + | ||||
| 1 | SSR-240612 | Drug Info | [1], [7] | |||
| 2 | Ac-Lys-[Leu(8)]-des-Arg(9)-BK | Drug Info | [9] | |||
| 3 | Des-Arg(9)-[Leu(8)]-BK | Drug Info | [10] | |||
| 4 | NVP-SAA164 | Drug Info | [13] | |||
| Inhibitor | [+] 6 Inhibitor drugs | + | ||||
| 1 | Des-Arg10-Kallidin | Drug Info | [11] | |||
| 2 | Des-Arg10-Leu9-Kallidin | Drug Info | [11] | |||
| 3 | H-DArg-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH(JMV1638) | Drug Info | [12] | |||
| 4 | H-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH(JMV1645) | Drug Info | [12] | |||
| 5 | H-Lys-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-OH(JMV1669) | Drug Info | [12] | |||
| 6 | JMV1431 | 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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| Calcium signaling pathway | hsa04020 | 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 | ||
| Complement and coagulation cascades | hsa04610 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Inflammatory mediator regulation of TRP channels | hsa04750 | Affiliated Target |
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| Class: Organismal Systems => Sensory system | Pathway Hierarchy | ||
| Regulation of actin cytoskeleton | hsa04810 | Affiliated Target |
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| Class: Cellular Processes => Cell motility | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.69E-01 | Radiality | 1.27E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.20E+01 | Topological coefficient | 1.00E+00 | 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 | ||
| 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 | [+] 6 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| 3 | Complement and coagulation cascades | |||||
| 4 | Inflammatory mediator regulation of TRP channels | |||||
| 5 | Regulation of actin cytoskeleton | |||||
| 6 | Pathways in cancer | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | Leptin Signaling Pathway | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (q) signalling events | |||||
| 3 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 9 WikiPathways | + | ||||
| 1 | Complement and Coagulation Cascades | |||||
| 2 | ACE Inhibitor Pathway | |||||
| 3 | Regulation of Actin Cytoskeleton | |||||
| 4 | GPCRs, Class A Rhodopsin-like | |||||
| 5 | Vitamin D Receptor Pathway | |||||
| 6 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 7 | Peptide GPCRs | |||||
| 8 | GPCR ligand binding | |||||
| 9 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | The kinin B1 receptor antagonist SSR240612 reverses tactile and cold allodynia in an experimental rat model of insulin resistance. Br J Pharmacol. 2007 September; 152(2): 280-287. | |||||
| REF 2 | ClinicalTrials.gov (NCT01319487) Safety and Efficacy Study of Topical Administration of FOV2304 (High Dose or Low Dose) for the Treatment of Center-involving Clinically Significant Macular Edema Associated With Diabetic Retinopathy. 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: 662). | |||||
| 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 800017078) | |||||
| REF 5 | ClinicalTrials.gov (NCT01207973) Safety, Tolerability, Pharmacokinetics and -Dynamics of Multiple Rising Oral Doses of BI 113823 in Patients Patients With Osteoarthritis of the Knee. U.S. National Institutes of Health. | |||||
| REF 6 | The role of kinin receptors in cancer and therapeutic opportunities. Cancer Letters Volume 345, Issue 1, 1 April 2014, Pages 27-38. | |||||
| REF 7 | Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36. | |||||
| REF 8 | The bradykinin B1 receptor antagonist BI113823 reverses inflammatory hyperalgesia by desensitization of peripheral and spinal neurons. Eur J Pain. 2015 Jan;19(1):132-42. | |||||
| REF 9 | Non-competitive pharmacological antagonism at the rabbit B(1) receptor. Br J Pharmacol. 2000 Nov;131(5):885-92. | |||||
| REF 10 | Evidence for the participation of kinins in Freund's adjuvant-induced inflammatory and nociceptive responses in kinin B1 and B2 receptor knockout mice. Neuropharmacology. 2001 Dec;41(8):1006-12. | |||||
| REF 11 | Development of an efficient and selective radioligand for bradykinin B1 receptor occupancy studies. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6045-8. | |||||
| REF 12 | Synthesis and biological evaluation of bradykinin B(1)/B(2) and selective B(1) receptor antagonists. J Med Chem. 2000 Jun 15;43(12):2382-6. | |||||
| REF 13 | 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: 659). | |||||
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