Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM4R6UV)

• Drug Name: BRADYKININ Drug Info
• Synonyms: BRADYKININ; Kallidin I; 58-82-2; L-Bradykinin; Synthetic bradykinin; Bradykinin (synthetic); Callidin I; UNII-S8TIM42R2W; Kallidin 9; BRS 640; PRS 640; S8TIM42R2W; CHEBI:3165; CHEMBL406291; Bradykinin, Lysyl; BK; Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg; EINECS 200-398-8; L-arginyl-L-prolyl-L-prolylglycyl-L-phenylalanyl-L-seryl-L-prolyl-L-phenylalanyl-L-arginine
• Cross-matching ID:
  PubChem CID: 439201
  ChEBI ID: CHEMBL406291
  CAS Number: CAS 58-82-2
  TTD Drug ID: DM4R6UV
  INTEDE Drug ID: DR1812

Molecule-Related Drug Atlas

Drug(s) Targeting B2 bradykinin receptor (BDKRB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Icatibant	DMQPTOZ	Hereditary angioedema	4A00.14	Approved	[12]
Fasitibant chloride	DM563NC	Osteoarthritis	FA00-FA05	Phase 2	[13]
DELTIBANT	DM5CB8U	Sepsis	1G40-1G41	Phase 2	[14]
Anatibant	DMG7IEN	Traumatic brain injury	NA07.Z	Phase 2	[15]
DM199	DM0157T	Cerebral ischemia	8B11	Phase 2	[16]
NPC-567	DMAVZ1F	Rhinitis	FA20	Discontinued in Phase 2	[17]
Labradimil	DMSFL76	Brain cancer	2A00	Discontinued in Phase 2	[18]
NPC-17731	DMGVIZY	Asthma	CA23	Terminated	[19]
JSM-10292	DMU5TGC	Pain	MG30-MG3Z	Terminated	[20]
CP-0597	DMS23JX	Asthma	CA23	Terminated	[21]

Drug(s) Metabolized By Angiotensin-converting enzyme 2 (ACE2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Angiotensin-(1-7)	DM76GZ0	Sarcoma	2A60-2C35	Phase 3	[22]

Drug(s) Metabolized By Carboxypeptidase M (CPM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epidermal growth factor	DMVONE6	Vulnerary	ND56.Z	Approved	[23]

Drug(s) Metabolized By Prolyl endopeptidase (PREP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gonadorelin	DMAQ469	Amenorrhea	GA20.0	Approved	[24]

Drug(s) Metabolized By Thimet oligopeptidase (THOP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Gonadorelin	DMAQ469	Amenorrhea	GA20.0	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
B2 bradykinin receptor (BDKRB2)	TTGY8IW	BKRB2_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cathepsin K (CTSK)	DEG3S8C	CATK_HUMAN	Substrate	[2]
Angiotensin-converting enzyme 2 (ACE2)	DEGPI81	ACE2_HUMAN	Substrate	[3]
Arginine carboxypeptidase (CPN1)	DEPWYLT	CBPN_HUMAN	Substrate	[4]
Soluble aminopeptidase P (sAmp)	DE8E6X9	XPP1_HUMAN	Substrate	[5]
Carboxypeptidase M (CPM)	DE1TNRG	CBPM_HUMAN	Substrate	[6]
Cathepsin H (CTSH)	DEHEZPI	CATH_HUMAN	Substrate	[7]
Dipeptidyl peptidase II (DPP7)	DEIORCK	DPP2_HUMAN	Substrate	[8]
PABA peptide hydrolase (MEP1B)	DEKBXUC	MEP1B_HUMAN	Substrate	[9]
Prolyl endopeptidase (PREP)	DEVSCNZ	PPCE_HUMAN	Substrate	[10]
Thimet oligopeptidase (THOP1)	DE95LJC	THOP1_HUMAN	Substrate	[11]

References

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• [2] A cysteine-type carboxypeptidase, cathepsin X, generates peptide receptor agonists. Int Immunopharmacol. 2010 Jan;10(1):134-9.
• [3] Nunn's Applied Respiratory Physiology (Eighth Edition). Chapter 11 - Nonrespiratory Functions of the Lung.2017, Pages 203-214.e2
• [4] Regulation of chemerin bioactivity by plasma carboxypeptidase N, carboxypeptidase B (activated thrombin-activable fibrinolysis inhibitor), and platelets. J Biol Chem. 2009 Jan 9;284(2):751-8.
• [5] Cloning, expression, and characterization of human cytosolic aminopeptidase P: a single manganese(II)-dependent enzyme. Biochemistry. 2000 Dec 12;39(49):15121-8.
• [6] Interactions between carboxypeptidase M and kinin B1 receptor in endothelial cells. Inflamm Res. 2019 Oct;68(10):845-855.
• [7] Human brain cathepsin H as a neuropeptide and bradykinin metabolizing enzyme. Peptides. 2003 Dec;24(12):1977-84.
• [8] Purification of two dipeptidyl aminopeptidases II from rat brain and their action on proline-containing neuropeptides. J Neurochem. 1989 Apr;52(4):1284-93.
• [9] Human and mouse homo-oligomeric meprin A metalloendopeptidase: substrate and inhibitor specificities. Biol Chem. 2007 Nov;388(11):1163-72.
• [10] Bradykinin release and inactivation in brain of rats submitted to an experimental model of Alzheimer's disease. Peptides. 2006 Dec;27(12):3363-9.
• [11] Expression and activity of thimet oligopeptidase (TOP) are modified in the hippocampus of subjects with temporal lobe epilepsy (TLE). Epilepsia. 2014 May;55(5):754-62.
• [12] Bradykinin receptor antagonists--a review of the patent literature 2005-2008. Expert Opin Ther Pat. 2009 Jul;19(7):919-41.
• [13] Fasitibant 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.
• [14] CP-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.
• [15] Inhibition 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.
• [16] Pharmacological effects of recombinant human tissue kallikrein on bradykinin B2 receptors. Pharmacol Res Perspect. 2015 Mar;3(2):e00119.
• [17] 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... J Med Chem. 2008 Nov 27;51(22):7094-8.
• [18] Metabolically 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.
• [19] Antinociceptive profile of the pseudopeptide B2 bradykinin receptor antagonist NPC 18688 in mice. Br J Pharmacol. 1996 Feb;117(3):552-558.
• [20] Binding characteristics of [3H]-JSM10292: a new cell membrane-permeant non-peptide bradykinin B2 receptor antagonist. Br J Pharmacol. 2012 Oct;167(4):839-53.
• [21] CP-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.
• [22] Metabolism of angiotensin-(1-7) by angiotensin-converting enzyme. Hypertension. 1998 Jan;31(1 Pt 2):362-7.
• [23] Extracellular conversion of epidermal growth factor (EGF) to des-Arg53-EGF by carboxypeptidase M. J Biol Chem. 1995 Jul 21;270(29):17154-8.
• [24] Ion-exchange chromatography: basic principles and application to the partial purification of soluble mammalian prolyl oligopeptidase. Methods Mol Biol. 2011;681:215-28.
• [25] Sleep deprivation changes thimet oligopeptidase (THOP1) expression and activity in rat brain. Heliyon. 2019 Nov 26;5(11):e02896.