Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOA9D3W)

• DOT Name: B2 bradykinin receptor (BDKRB2)
• Synonyms: B2R; BK-2 receptor
• Gene Name: BDKRB2
• UniProt ID: BKRB2_HUMAN
• PDB ID: 7F2O; 7F6H; 7F6I
• Pfam ID: PF00001
• Sequence:
  MFSPWKISMFLSVREDSVPTTASFSADMLNVTLQGPTLNGTFAQSKCPQVEWLGWLNTIQ
  PPFLWVLFVLATLENIFVLSVFCLHKSSCTVAEIYLGNLAAADLILACGLPFWAITISNN
  FDWLFGETLCRVVNAIISMNLYSSICFLMLVSIDRYLALVKTMSMGRMRGVRWAKLYSLV
  IWGCTLLLSSPMLVFRTMKEYSDEGHNVTACVISYPSLIWEVFTNMLLNVVGFLLPLSVI
  TFCTMQIMQVLRNNEMQKFKEIQTERRATVLVLVVLLLFIICWLPFQISTFLDTLHRLGI
  LSSCQDERIIDVITQIASFMAYSNSCLNPLVYVIVGKRFRKKSWEVYQGVCQKGGCRSEP
  IQMENSMGTLRTSISVERQIHKLQDWAGSRQ
• Function: Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
• Tissue Specificity: Ubiquitous. Widespread in normal smooth muscle tissue and neurons.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  cGMP-PKG sig.ling pathway (hsa04022)
  Sphingolipid sig.ling pathway (hsa04071)
  Neuroactive ligand-receptor interaction (hsa04080)
  Complement and coagulation cascades (hsa04610)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Regulation of actin cytoskeleton (hsa04810)
  Endocrine and other factor-regulated calcium reabsorption (hsa04961)
  Chagas disease (hsa05142)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (i) signalling events (R-HSA-418594)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 11 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Indomethacin	DMSC4A7	Approved	B2 bradykinin receptor (BDKRB2) increases the Enterocolitis ADR of Indomethacin.	[15]
Atenolol	DMNKG1Z	Approved	B2 bradykinin receptor (BDKRB2) affects the response to substance of Atenolol.	[16]
Enalapril	DMNFUZR	Approved	B2 bradykinin receptor (BDKRB2) increases the Cough ADR of Enalapril.	[15]
Perindopril	DMOPZDT	Approved	B2 bradykinin receptor (BDKRB2) increases the Cough ADR of Perindopril.	[15]
Captopril	DM458UM	Approved	B2 bradykinin receptor (BDKRB2) increases the Cough ADR of Captopril.	[15]
Ramipril	DM2R68E	Approved	B2 bradykinin receptor (BDKRB2) increases the Cough ADR of Ramipril.	[15]
Fosinopril	DM9NJ52	Approved	B2 bradykinin receptor (BDKRB2) increases the Cough ADR of Fosinopril.	[15]
Trandolapril	DM4L6EU	Approved	B2 bradykinin receptor (BDKRB2) increases the Cough ADR of Trandolapril.	[15]
Quinapril	DMR8H31	Approved	B2 bradykinin receptor (BDKRB2) increases the Cough ADR of Quinapril.	[15]
Irbesartan	DMTP1DC	Investigative	B2 bradykinin receptor (BDKRB2) affects the response to substance of Irbesartan.	[16]
Lisinopril	DMUOK4C	Investigative	B2 bradykinin receptor (BDKRB2) increases the Cough ADR of Lisinopril.	[15]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of B2 bradykinin receptor (BDKRB2).	[1]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of B2 bradykinin receptor (BDKRB2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of B2 bradykinin receptor (BDKRB2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of B2 bradykinin receptor (BDKRB2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of B2 bradykinin receptor (BDKRB2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of B2 bradykinin receptor (BDKRB2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of B2 bradykinin receptor (BDKRB2).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of B2 bradykinin receptor (BDKRB2).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of B2 bradykinin receptor (BDKRB2).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of B2 bradykinin receptor (BDKRB2).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of B2 bradykinin receptor (BDKRB2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of B2 bradykinin receptor (BDKRB2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of B2 bradykinin receptor (BDKRB2).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of B2 bradykinin receptor (BDKRB2).	[14]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [15] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [16] B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. J Hypertens. 2003 Mar;21(3):621-4. doi: 10.1097/00004872-200303000-00029.