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
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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 | ||||
| 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] | |||
| 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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