Details of the Drug

General Information of Drug (ID: DMRK8OT)

Drug Name
Candesartan
Synonyms
candesartan; 139481-59-7; Blopress; Ratacand; CV-11974; 1-((2'-(1H-Tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylic acid; CV 11974; UNII-S8Q36MD2XX; 2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid; CHEMBL1016; S8Q36MD2XX; 2-Ethoxy-1-(p-(o-1H-tetrazol-5-ylphenyl)benzyl)-7-benzimidazolecarboxylic acid; CHEBI:3347; C24H20N6O3; 2-ethoxy-3-[[4-[2-(1h-tetrazol-5-yl)phenyl]phenyl]methyl]-3h-benzoimidazole-4-carboxylic acid; NCGC00167474-01; AK-57139; Blopress; Candesartan [BAN]; CV11974; Amias (TN); Atacand (TN); Blopress (TN); Candesartan [USAN:INN]; KS-5003; Ratacand (TN); Candesartan (USAN/INN); Atacand, Blopress, Amias, Ratacand,Candesartan; 2-(ethyloxy)-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid; 2-Ethoxy-3-[[4-[2-(1H-tetrazol-5-yl)phenyl]phenyl] methyl]-3H-benzoimidazole-4-carboxylic acid; 2-ethoxy-1-({2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl}methyl)-1H-benzimidazole-7-carboxylic acid; 2-ethoxy-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid; 2-ethoxy-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4ethyl}-1H-benzimidazole-7-carboxylic acid; 2-ethoxy-7-carboxy-1-(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methylbenzimidazole; [3H]candesartan
Indication
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [1]
Hypertension BA00-BA04 Approved [2]
Malignant essential hypertension BA00 Approved [1]
Therapeutic Class
Antihypertensive Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 440.5
Logarithm of the Partition Coefficient (xlogp) 4.1
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [3]
Elimination
0% of drug is excreted from urine in the unchanged form [3]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.60618 micromolar/kg/day [4]
Water Solubility
The ability of drug to dissolve in water is measured as 0.05 mg/mL [3]
Chemical Identifiers
Formula
C24H20N6O3
IUPAC Name
2-ethoxy-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylic acid
Canonical SMILES
CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NNN=N5)C(=O)O
InChI
InChI=1S/C24H20N6O3/c1-2-33-24-25-20-9-5-8-19(23(31)32)21(20)30(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-26-28-29-27-22/h3-13H,2,14H2,1H3,(H,31,32)(H,26,27,28,29)
InChIKey
HTQMVQVXFRQIKW-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
2541
ChEBI ID
CHEBI:3347
CAS Number
139481-59-7
DrugBank ID
DB13919
TTD ID
D0D5SQ
VARIDT ID
DR00601
INTEDE ID
DR0264
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Angiotensin II receptor type-1 (AGTR1) TT8DBY3 AGTR1_HUMAN Antagonist [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [6]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Substrate [7]
Prostaglandin G/H synthase 1 (COX-1) DE073H6 PGH1_HUMAN Substrate [8]
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Substrate [9]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DEF2WXN UD13_HUMAN Substrate [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Adiponectin (ADIPOQ) OTNX23LE ADIPO_HUMAN Gene/Protein Processing [10]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Gene/Protein Processing [11]
Carbonic anhydrase 1 (CA1) OTNFBVVQ CAH1_HUMAN Gene/Protein Processing [12]
CD40 ligand (CD40LG) OT75Z6A6 CD40L_HUMAN Gene/Protein Processing [10]
Cytochrome b-245 light chain (CYBA) OT16N9ZO CY24A_HUMAN Gene/Protein Processing [13]
Cytochrome P450 11B2, mitochondrial (CYP11B2) OTIOLWYN C11B2_HUMAN Drug Response [14]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Gene/Protein Processing [15]
Leptin (LEP) OT5Q7ODW LEP_HUMAN Gene/Protein Processing [16]
NADPH oxidase 4 (NOX4) OTTYQ097 NOX4_HUMAN Gene/Protein Processing [13]
Platelet glycoprotein 4 (CD36) OT5CZWKY CD36_HUMAN Gene/Protein Processing [17]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Chronic heart failure
ICD Disease Classification BD1Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Angiotensin II receptor type-1 (AGTR1) DTT AGTR1 8.95E-01 1.34E-02 0.07
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME UGT1A1 1.10E-01 -5.91E-02 -3.60E-01
Carboxylesterase 1 (CES1) DME CES1 2.02E-01 -7.66E-03 -1.88E-02
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 1.90E-01 -9.81E-03 -5.96E-02
Prostaglandin G/H synthase 1 (COX-1) DME PTGS1 3.97E-03 1.56E-01 4.33E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Candesartan FDA Label
2 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: 587).
3 BDDCS applied to over 900 drugs
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 Candesartan: widening indications for this angiotensin II receptor blocker Expert Opin Pharmacother. 2009 Aug;10(12):1995-2007.
6 Product Monograph of Atacand.
7 The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards N2 in the tetrazole ring of losartan, candesartan, and zolarsartan. Biochem Pharmacol. 2008 Sep 15;76(6):763-72.
8 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
9 Different hydrolases involved in bioactivation of prodrug-type angiotensin receptor blockers: carboxymethylenebutenolidase and carboxylesterase 1. Drug Metab Dispos. 2013 Nov;41(11):1888-95.
10 Additive beneficial effects of fenofibrate combined with candesartan in the treatment of hypertriglyceridemic hypertensive patients. Diabetes Care. 2006 Feb;29(2):195-201. doi: 10.2337/diacare.29.02.06.dc05-1418.
11 Candesartan reduces oxidative stress and inflammation in patients with essential hypertension. Hypertens Res. 2003 Sep;26(9):691-7. doi: 10.1291/hypres.26.691.
12 The mechanism of action of angiotensin II is dependent on direct activation of vascular smooth muscle carbonic anhydrase I. Int J Clin Lab Res. 2000;30(3):119-25. doi: 10.1007/s005990070010.
13 Protective mechanisms of the angiotensin II type 1 receptor blocker candesartan against cerebral ischemia: in-vivo and in-vitro studies. J Hypertens. 2008 Jul;26(7):1435-45. doi: 10.1097/HJH.0b013e3283013b6e.
14 Variants of the CYP11B2 gene predict response to therapy with candesartan. Eur J Pharmacol. 2002 Jun 7;445(1-2):151-2. doi: 10.1016/s0014-2999(02)01766-1.
15 Angiotensin II type 1 receptor antagonist candesartan as an angiogenic inhibitor in a xenograft model of bladder cancer. Clin Cancer Res. 2006 May 1;12(9):2888-93. doi: 10.1158/1078-0432.CCR-05-2213.
16 Distinct vascular and metabolic effects of different classes of anti-hypertensive drugs. Int J Cardiol. 2010 Apr 1;140(1):73-81. doi: 10.1016/j.ijcard.2008.11.017. Epub 2008 Dec 6.
17 Telmisartan ameliorates lipopolysaccharide-induced innate immune response through peroxisome proliferator-activated receptor- activation in human monocytes. J Hypertens. 2012 Jan;30(1):87-96. doi: 10.1097/HJH.0b013e32834dde5f.