Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1DHSVQ)

• DOT Name: B1 bradykinin receptor (BDKRB1)
• Synonyms: B1R; BK-1 receptor
• Gene Name: BDKRB1
• UniProt ID: BKRB1_HUMAN
• PDB ID: 7EIB
• Pfam ID: PF00001
• Sequence:
  MASSWPPLELQSSNQSQLFPQNATACDNAPEAWDLLHRVLPTFIISICFFGLLGNLFVLL
  VFLLPRRQLNVAEIYLANLAASDLVFVLGLPFWAENIWNQFNWPFGALLCRVINGVIKAN
  LFISIFLVVAISQDRYRVLVHPMASRRQQRRRQARVTCVLIWVVGGLLSIPTFLLRSIQA
  VPDLNITACILLLPHEAWHFARIVELNILGFLLPLAAIVFFNYHILASLRTREEVSRTRC
  GGRKDSKTTALILTLVVAFLVCWAPYHFFAFLEFLFQVQAVRGCFWEDFIDLGLQLANFF
  AFTNSSLNPVIYVFVGRLFRTKVWELYKQCTPKSLAPISSSHRKEIFQLFWRN
• Function: This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Complement and coagulation cascades (hsa04610)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Regulation of actin cytoskeleton (hsa04810)
  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

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 B1 bradykinin receptor (BDKRB1).	[1]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of B1 bradykinin receptor (BDKRB1).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of B1 bradykinin receptor (BDKRB1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of B1 bradykinin receptor (BDKRB1).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of B1 bradykinin receptor (BDKRB1).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of B1 bradykinin receptor (BDKRB1).	[5]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of B1 bradykinin receptor (BDKRB1).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of B1 bradykinin receptor (BDKRB1).	[7]
Enalaprilat	DMFYAM1	Approved	Enalaprilat increases the activity of B1 bradykinin receptor (BDKRB1).	[8]
Beclomethasone dipropionate	DM5NW1E	Phase 4	Beclomethasone dipropionate decreases the expression of B1 bradykinin receptor (BDKRB1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of B1 bradykinin receptor (BDKRB1).	[11]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of B1 bradykinin receptor (BDKRB1).	[13]
Anandamide	DMCKH3P	Investigative	Anandamide decreases the activity of B1 bradykinin receptor (BDKRB1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of B1 bradykinin receptor (BDKRB1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of B1 bradykinin receptor (BDKRB1).	[12]

References

• [1] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [2] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [6] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Novel mode of action of angiotensin I converting enzyme inhibitors: direct activation of bradykinin B1 receptor. J Biol Chem. 2002 May 10;277(19):16847-52. doi: 10.1074/jbc.M200355200. Epub 2002 Mar 5.
• [9] Comparison of kinin B(1) and B(2) receptor expression in neutrophils of asthmatic and non-asthmatic subjects. Int Immunopharmacol. 2007 Dec 20;7(14):1862-8. doi: 10.1016/j.intimp.2007.07.012. Epub 2007 Aug 6.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [14] The endocannabinoid anandamide inhibits kinin B1 receptor sensitization through cannabinoid CB1 receptor stimulation in human umbilical vein. Eur J Pharmacol. 2009 Jan 5;602(1):176-9. doi: 10.1016/j.ejphar.2008.10.058. Epub 2008 Nov 11.