Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTG5QIA)

• DTT Name: B1 bradykinin receptor (BDKRB1)
• Synonyms: BRADYB1; BK-1 receptor; B1R
• Gene Name: BDKRB1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: BKRB1_HUMAN
• TTD ID: T58589
• 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 signaling 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 DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Safotibant	DMKDP57	Diabetic macular edema	9B71.02	Phase 2	[2]
SSR-240612	DMFNZPY	Rheumatoid arthritis	FA20	Phase 2	[1]
BI 113823	DMUJ1EL	Osteoarthritis	FA00-FA05	Phase 1	[3]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ac-Lys-[Leu(8)]-des-Arg(9)-BK	DMIAYTP	Discovery agent	N.A.	Investigative	[4]
Des-Arg(9)-[Leu(8)]-BK	DMVX9I0	Depression	6A70-6A7Z	Investigative	[5]
Des-Arg10-Kallidin	DMZ5Y94	Discovery agent	N.A.	Investigative	[6]
Des-Arg10-Leu9-Kallidin	DMWO4EI	Discovery agent	N.A.	Investigative	[6]
H-DArg-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH(JMV1638)	DM6839G	Discovery agent	N.A.	Investigative	[7]
H-Lys-Arg-Pro-Hyp-Gly-Igl-Ser-D-BT-OH(JMV1645)	DMDXIS7	Discovery agent	N.A.	Investigative	[7]
H-Lys-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-OH(JMV1669)	DMTGU0L	Discovery agent	N.A.	Investigative	[7]
JMV1431	DMAR3M2	Discovery agent	N.A.	Investigative	[7]
NVP-SAA164	DMN90R6	Pain	MG30-MG3Z	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Osteoarthritis	FA20	Synovial tissue	2.86E-01	0.54	0.35
Rheumatoid arthritis	FA20	Synovial tissue	4.33E-03	1.25E-03	1.73E-03

References

• [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.
• [2] The role of kinin receptors in cancer and therapeutic opportunities. Cancer Letters Volume 345, Issue 1, 1 April 2014, Pages 27-38.
• [3] 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.
• [4] Non-competitive pharmacological antagonism at the rabbit B(1) receptor. Br J Pharmacol. 2000 Nov;131(5):885-92.
• [5] 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.
• [6] Development of an efficient and selective radioligand for bradykinin B1 receptor occupancy studies. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6045-8.
• [7] 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.
• [8] 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).