Details of the Drug

General Information of Drug (ID: DM4R6UV)

• Drug Name: BRADYKININ
• 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
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 1060.2
  Logarithm of the Partition Coefficient (xlogp); -4.8
  Rotatable Bond Count (rotbonds); 27
  Hydrogen Bond Donor Count (hbonddonor); 12
  Hydrogen Bond Acceptor Count (hbondacc); 14
• Chemical Identifiers:
  Formula: C50H73N15O11
  IUPAC Name: (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid
  Canonical SMILES: C1C[C@H](N(C1)C(=O)[C@@H]2CCCN2C(=O)[C@H](CCCN=C(N)N)N)C(=O)NCC(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CO)C(=O)N4CCC[C@H]4C(=O)N[C@@H](CC5=CC=CC=C5)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O
  InChI: InChI=1S/C50H73N15O11/c51-32(16-7-21-56-49(52)53)45(72)65-25-11-20-39(65)47(74)64-24-9-18-37(64)43(70)58-28-40(67)59-34(26-30-12-3-1-4-13-30)41(68)62-36(29-66)46(73)63-23-10-19-38(63)44(71)61-35(27-31-14-5-2-6-15-31)42(69)60-33(48(75)76)17-8-22-57-50(54)55/h1-6,12-15,32-39,66H,7-11,16-29,51H2,(H,58,70)(H,59,67)(H,60,69)(H,61,71)(H,62,68)(H,75,76)(H4,52,53,56)(H4,54,55,57)/t32-,33-,34-,35-,36-,37-,38-,39-/m0/s1
  InChIKey: QXZGBUJJYSLZLT-FDISYFBBSA-N
• Cross-matching ID:
  PubChem CID: 439201
  ChEBI ID: CHEBI:3165
  CAS Number: 58-82-2
  DrugBank ID: DB12126
  TTD ID: D0X0BI
  INTEDE ID: DR1812

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]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Gene/Protein Processing	[12]

Molecular Expression Atlas of This Drug

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
B2 bradykinin receptor (BDKRB2)	DTT	BDKRB2	6.64E-04	-0.24	-0.54
Prolyl endopeptidase (PREP)	DME	PREP	2.85E-01	-8.06E-02	-1.15E-01
Arginine carboxypeptidase (CPN1)	DME	CPN1	6.02E-16	-1.48E-01	-4.63E-01
PABA peptide hydrolase (MEP1B)	DME	MEP1B	5.94E-07	-1.76E-01	-4.20E-01
Dipeptidyl peptidase II (DPP7)	DME	DPP7	2.50E-59	4.02E-01	1.17E+00
Cathepsin H (CTSH)	DME	CTSH	5.92E-01	-8.46E-02	-1.10E-01
Angiotensin-converting enzyme 2 (ACE2)	DME	ACE2	6.32E-01	6.30E-03	2.97E-02
Cathepsin K (CTSK)	DME	CTSK	3.42E-104	1.01E+00	1.64E+00
Thimet oligopeptidase (THOP1)	DME	THOP1	2.83E-06	-1.78E-01	-4.15E-01
Soluble aminopeptidase P (sAmp)	DME	XPNPEP1	6.11E-02	-8.81E-02	-1.40E-01
Carboxypeptidase M (CPM)	DME	CPM	6.33E-05	1.36E-01	2.10E-01

References

• [1] 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.
• [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 stimulation of nitric oxide production is not sufficient for gamma-globin induction. Srp Arh Celok Lek. 2014 Mar-Apr;142(3-4):189-96. doi: 10.2298/sarh1404189c.