Target Information

Target General Infomation
Target ID
T23714
Former ID
TTDC00111
Target Name
B2 bradykinin receptor
Gene Name
BDKRB2
Synonyms
B2R; BK B(2) receptor; BK-2 receptor; Bradykinin B2 receptor; BDKRB2
Target Type
Successful
Disease Asthma [ICD10: J45]
Brain cancer [ICD9: 191, 225.0; ICD10: C71, D33]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Hereditary angioedema [ICD9: 277.6; ICD10: D84.1]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Osteoarthritis [ICD9: 715; ICD10: M15-M19, M47]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Rhinitis [ICD9: 472.0, 477; ICD10: J00, J30, J31.0]
Septic shock [ICD9: 785.52; ICD10: A41.9]
Traumatic brain injury [ICD9: 800.0-801.9, 803.0-804.9, 850.0-854.1; ICD10: S06]
Unspecified [ICD code not available]
Function
Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
BioChemical Class
GPCR rhodopsin
Target Validation
T23714
UniProt ID
P30411
Sequence
MFSPWKISMFLSVREDSVPTTASFSADMLNVTLQGPTLNGTFAQSKCPQVEWLGWLNTIQ
PPFLWVLFVLATLENIFVLSVFCLHKSSCTVAEIYLGNLAAADLILACGLPFWAITISNN
FDWLFGETLCRVVNAIISMNLYSSICFLMLVSIDRYLALVKTMSMGRMRGVRWAKLYSLV
IWGCTLLLSSPMLVFRTMKEYSDEGHNVTACVISYPSLIWEVFTNMLLNVVGFLLPLSVI
TFCTMQIMQVLRNNEMQKFKEIQTERRATVLVLVVLLLFIICWLPFQISTFLDTLHRLGI
LSSCQDERIIDVITQIASFMAYSNSCLNPLVYVIVGKRFRKKSWEVYQGVCQKGGCRSEP
IQMENSMGTLRTSISVERQIHKLQDWAGSRQ
Drugs and Mode of Action
Drug(s) Icatibant Drug Info Approved Hereditary angioedema [1], [2], [3]
Anatibant Drug Info Phase 2 Traumatic brain injury [4], [5]
DELTIBANT Drug Info Phase 2 Septic shock [6]
Fasitibant chloride Drug Info Phase 2 Osteoarthritis [7]
BRADYKININ Drug Info Phase 1 Discovery agent [8], [9]
Labradimil Drug Info Discontinued in Phase 2 Brain cancer [10], [11]
NPC-567 Drug Info Discontinued in Phase 2 Rhinitis [12], [13]
CP-0597 Drug Info Terminated Asthma [14]
FR-172357 Drug Info Terminated Inflammatory disease [15]
FR-173657 Drug Info Terminated Discovery agent [16], [17]
JSM-10292 Drug Info Terminated Pain [18]
NPC-17731 Drug Info Terminated Asthma [19], [20]
Inhibitor (D)Arg-Arg-Pro-Hyp-Gly-Phe-Ser-(d)Phe-Phe-Arg Drug Info [21]
(D)Arg-Arg-Pro-Hyp-Gly-Thi-Cys-(D)Phe-Phe-Cys-Arg Drug Info [21]
(D)Arg-Arg-Pro-Hyp-Gly-Thi-Ser-(D)Tic-Aoc-Arg Drug Info [21]
(D)Arg-Arg-Pro-Hyp-Gly-Thi-Ser-(D)Tic-Tic-Arg Drug Info [21]
BRADYKININ Drug Info [22]
FR-173657 Drug Info [23]
H-DArg-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH(JMV1638) Drug Info [22]
H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-OH(JMV1431) Drug Info [22]
H-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH(JMV1645) Drug Info [22]
H-Lys-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-OH(JMV1669) Drug Info [22]
NPC-567 Drug Info [24]
Quinapril analogue Drug Info [25]
Antagonist Anatibant Drug Info [26], [27]
bradyzide Drug Info [28]
chroman 28 Drug Info [29]
compound 11 Drug Info [30]
compound 12 Drug Info [31]
CP-0597 Drug Info [32]
Fasitibant chloride Drug Info [33]
FR-172357 Drug Info [34]
FR167344 Drug Info [35]
Icatibant Drug Info [36], [37], [38]
JMV1431 Drug Info [22]
JSM-10292 Drug Info [39]
NPC-17731 Drug Info [40]
NPC-349 Drug Info [41]
PS020990 Drug Info [42]
WIN 64338 Drug Info [43]
Modulator Breceptin Drug Info [44]
DELTIBANT Drug Info [6]
LF-160335 Drug Info [45]
Agonist FR190997 Drug Info [46]
FR191413 Drug Info [47]
kallidin Drug Info [41]
Labradimil Drug Info [48], [49]
Met-Lys-bradykinin Drug Info [50]
T-kinin Drug Info [51]
[des-Arg9]bradykinin Drug Info [52]
[Leu8,des-Arg9]bradykinin Drug Info [53]
[Sar,D-Phe8,des-Arg9]bradykinin Drug Info [51]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Calcium signaling pathway
cGMP-PKG signaling pathway
Sphingolipid signaling pathway
Neuroactive ligand-receptor interaction
Complement and coagulation cascades
Inflammatory mediator regulation of TRP channels
Regulation of actin cytoskeleton
Endocrine and other factor-regulated calcium reabsorption
Chagas disease (American trypanosomiasis)
Pathways in cancer
NetPath Pathway TGF_beta_Receptor Signaling Pathway
PANTHER Pathway Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
Pathway Interaction Database Direct p53 effectors
Validated transcriptional targets of deltaNp63 isoforms
Reactome Peptide ligand-binding receptors
G alpha (q) signalling events
G alpha (i) signalling events
WikiPathways ACE Inhibitor Pathway
Regulation of Actin Cytoskeleton
GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
Nifedipine Activity
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
References
REF 12011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
REF 2Icatibant , the bradykinin B2 receptor antagonist with target to the interconnected kinin systems. Expert Opin Pharmacother. 2012 Oct;13(15):2233-47.
REF 3(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: 667).
REF 4Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs. 2009 Mar;14(1):67-84.
REF 5(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: 679).
REF 6CP-0127, a novel potent bradykinin antagonist, increases survival in rat and rabbit models of endotoxin shock. Agents Actions Suppl. 1992;38 ( Pt 3):413-20.
REF 7ClinicalTrials.gov (NCT01091116) A Locally Injected Bradykinin Antagonist for TReatment of OSteoarthritiS. U.S. National Institutes of Health.
REF 8ClinicalTrials.gov (NCT00868855) Tissue-Type Plasminogen Activator (t-PA) Release Predicts Major Adverse Cardiac Events (MACE) in Patients With Non-Critical Coronary Artery Disease. U.S. National Institutes of Health.
REF 9(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: 649).
REF 10(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: 672).
REF 11Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006912)
REF 12(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: 676).
REF 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002385)
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008984)
REF 15Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008533)
REF 16(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: 674).
REF 17Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007597)
REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024715)
REF 19(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: 657).
REF 20Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007977)
REF 21J Med Chem. 1991 Mar;34(3):1230-3.Design and conformational analysis of several highly potent bradykinin receptor antagonists.
REF 22J Med Chem. 2000 Jun 15;43(12):2382-6.Synthesis and biological evaluation of bradykinin B(1)/B(2) and selective B(1) receptor antagonists.
REF 23J Med Chem. 2009 Jul 23;52(14):4370-9.Novel small molecule bradykinin B2 receptor antagonists.
REF 24J Med Chem. 2008 Nov 27;51(22):7094-8.cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain responses against carrageenan-induced hyperalgesia.
REF 25Ace inhibitors as a template for the design of bradykinin B2 receptor antagonists, Bioorg. Med. Chem. Lett. 5(4):367-370 (1995).
REF 26Anatibant, a selective non-peptide bradykinin B2 receptor antagonist, reduces intracranial hypertension and histopathological damage after experimental traumatic brain injury. Neurosci Lett. 2009 Apr24;454(2):115-7. Epub 2009 Feb 11.
REF 27Inhibition of bradykinin B2 receptors before, not after onset of experimental subarachnoid hemorrhage prevents brain edema formation and improves functional outcome. Crit Care Med. 2009 Jul;37(7):2228-34.
REF 28Bradyzide, a potent non-peptide B(2) bradykinin receptor antagonist with long-lasting oral activity in animal models of inflammatory hyperalgesia. Br J Pharmacol. 2000 Jan;129(1):77-86.
REF 29Identification of a nonpeptidic and conformationally restricted bradykinin B1 receptor antagonist with anti-inflammatory activity. J Med Chem. 2007 Feb 22;50(4):607-10. Epub 2007 Jan 23.
REF 30Discovery of a potent, non-peptide bradykinin B1 receptor antagonist. J Am Chem Soc. 2003 Jun 25;125(25):7516-7.
REF 31Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem. 2003 May 8;46(10):1803-6.
REF 32CP-0597, a selective bradykinin B2 receptor antagonist, inhibits brain injury in a rat model of reversible middle cerebral artery occlusion. Stroke. 1997 Jul;28(7):1430-6.
REF 33Fasitibant chloride, a kinin B??receptor antagonist, and dexamethasone interact to inhibit carrageenan-induced inflammatory arthritis in rats. Br J Pharmacol. 2012 Jun;166(4):1403-10.
REF 34Characterization of FR 172357, a new non-peptide bradykinin B(2) receptor antagonist, in human, pig and rabbit preparations. Eur J Pharmacol. 1999 Dec 10;386(1):25-31.
REF 35Novel subtype-selective nonpeptide bradykinin receptor antagonists FR167344 and FR173657. Mol Pharmacol. 1997 Feb;51(2):171-6.
REF 36Bradykinin in the heart: friend or foe? Circulation. 1999 Dec 7;100(23):2305-7.
REF 37Pharmacological characterization of the bradykinin B2 receptor antagonist MEN16132 in rat in vitro bioassays. Eur J Pharmacol. 2009 Aug 1;615(1-3):10-6. Epub 2009 May 13.
REF 38Bradykinin receptor antagonists--a review of the patent literature 2005-2008. Expert Opin Ther Pat. 2009 Jul;19(7):919-41.
REF 39Binding characteristics of [3H]-JSM10292: a new cell membrane-permeant non-peptide bradykinin B2 receptor antagonist. Br J Pharmacol. 2012 Oct;167(4):839-53.
REF 40Antinociceptive profile of the pseudopeptide B2 bradykinin receptor antagonist NPC 18688 in mice. Br J Pharmacol. 1996 Feb;117(3):552-558.
REF 41Differential pharmacology of cloned human and mouse B2 bradykinin receptors. Mol Pharmacol. 1994 Jan;45(1):1-8.
REF 42Small molecule antagonists of the bradykinin B1 receptor. Immunopharmacology. 1999 Sep;43(2-3):169-77.
REF 43Design of potent non-peptide competitive antagonists of the human bradykinin B2 receptor. J Med Chem. 1993 Aug 20;36(17):2583-4.
REF 44(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: 42).
REF 45The ChEMBL database in 2017.
REF 46Nonpeptide mimic of bradykinin with long-acting properties at the bradykinin B2 receptor. Mol Pharmacol. 1997 Jul;52(1):16-20.
REF 47Discovery of the first non-peptide full agonists for the human bradykinin B(2) receptor incorporating 4-(2-picolyloxy)quinoline and 1-(2-picolyl)benzimidazole frameworks. J Med Chem. 2004 May 20;47(11):2853-63.
REF 48Bradykinin receptor agonist facilitates low-dose cyclosporine-A protection against 6-hydroxydopamine neurotoxicity. Brain Res. 2002 Nov 29;956(2):211-20.
REF 49Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life. J Transl Med. 2009 May 13;7:33.
REF 50Expression cloning of a human B1 bradykinin receptor. J Biol Chem. 1994 Aug 26;269(34):21583-6.
REF 51Molecular characterisation of cloned bradykinin B1 receptors from rat and human. Eur J Pharmacol. 1999 Jun 25;374(3):423-33.
REF 52Stable expression of human kinin B1 receptor in 293 cells: pharmacological and functional characterization. Br J Pharmacol. 1997 Sep;122(2):393-9.
REF 53Partial agonists and full antagonists at the human and murine bradykinin B1 receptors. Can J Physiol Pharmacol. 1997 Jun;75(6):735-40.

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