Drug Details

General Information of the Drug (ID: DR1895)
Name
Losartan
Synonyms
losartan; 114798-26-4; DUP 89; Lortaan; Cozaar; LOSARTAN POTASSIUM; Hyzaar; UNII-JMS50MPO89; CHEBI:6541; MK-954; JMS50MPO89; (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol; 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole; DTXSID7023227; DuP 753; MFCD00865831; [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol; NCGC00095125-01; Losartan [INN:BAN]; DSSTox_CID_3227; DSSTox_RID_76933; DSSTox_GSID_23227; (1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-butyl-4-chloro-1H-imidazol-5-yl)methanol; (1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-butyl-4-chloro-1H-imidazol-5-yl)methanol; [2-butyl-5-chloranyl-3-[[4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol; 1H-Imidazole-5-methanol, 2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)(1,1'- biphenyl)-4-yl)methyl)-; 1H-imidazole-5-methanol, 2-butyl-4-chloro-1-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-; C22H23ClN6O; (1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-4-chloro-1H-imidazol-5-yl)methanol; [3H]losartan; Losartan (INN); Losartic (TN); 2-BUTYL-4-CHLORO-1-[[2'-(1H-TETRAZOL-5-YL)[1,1'-BIPHENYL]-4-YL]METHYL]-1H-IMIDAZOLE-5-METHANOL; [3H]-losartan; CAS-114798-26-4; SR-01000763170; lorastan; 2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol; [2-butyl-5-chloro-3-[[4-[2-(1H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol; Losartan-[d3]; PubChem9176; Dup89; Spectrum_001713; SCHEMBL60; Spectrum2_001677; Spectrum3_000998; Spectrum4_001126; Spectrum5_001466; Epitope ID:140137; EC 601-329-8; Oprea1_644635; US9624243, Losartin; BSPBio_002695; GTPL590; KBioGR_001611; KBioSS_002193; (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl}-1H-imidazol-5-yl)methanol; BIDD:GT0286; SPECTRUM1504268; SPBio_001893; DUP-89; GTPL3941; BDBM82258; HSDB 7043; KBio2_002193; KBio2_004761; KBio2_007329; KBio3_001915; HGP1405; BCPP000183; BDBM318822; EX 89; HMS1922J13; HMS2093E22; HMS3715L11; Pharmakon1600-01504268; BCP27731; HGP-1405; NSC_3961; ZINC3873160; Tox21_111435; CCG-39095; NSC758699; s5067; STL419984; 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5ylphenyl)benzyl]imidazole-5-methanol; AKOS015917390; AKOS015994740; Tox21_111435_1; AB07507; BCP9000861; DB00678; KS-5004; MCULE-5204931675; NSC 758699; NSC-758699; (2-butyl-4-chloro-1-{[2'-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol; 2-n-butyl-4-chloro-5-hydroxymethyl-1-[[2'-(1H-tetrazol-5-yl)-biphenyl-4-yl]methyl]imidazole; NCGC00095125-02; NCGC00095125-03; NCGC00095125-05; NCGC00095125-08; [2-butyl-4-chloro-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazol-5-yl]methanol; 2-Butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl-1H-imidazole-5-methanol; AK326126; HY-17512; I497; SBI-0206766.P001; AB0013723; CAS_114798-26-4; FT-0631074; C07072; D08146; 54244-EP2269989A1; 54244-EP2270011A1; 54244-EP2272841A1; 54244-EP2277879A1; 54244-EP2287165A2; 54244-EP2287166A2; 54244-EP2292620A2; 54244-EP2295053A1; 54244-EP2295406A1; 54244-EP2298772A1; 54244-EP2298776A1; 54244-EP2298779A1; 54244-EP2301923A1; 54244-EP2301931A1; 54244-EP2301936A1; 54244-EP2305219A1; 54244-EP2308562A2; 54244-EP2308839A1; AB01563296_01; 798L264; A803239; L000351; Q410074; Q-201321; SR-01000763170-3; SR-01000763170-4; BRD-K76205745-001-02-5; BRD-K76205745-001-04-1; F2173-0506; [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]-4-imidazolyl]methanol; 2-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]imidazole; 2-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole; (1-((2'-(2h-tetrazol-5-yl)biphenyl-4-yl)methyl)-2-butyl-4-chloro-1h-imidazol-5-yl)methanol; {2-Butyl-5-chloro-3-[2'-(2H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-3H-imidazol-4-yl}-methanol; 1H-Imidazole-5-methanol, 2-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]- (9CI); 2-butyl-4-chloro-1-[[2'-(2h-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1h-imidazole-5-methanol; 2-butyl-4-chloro-1-[2'-(2H-tetrazol-5-yl)-1,1'-biphenyl-4-ylmethyl]-1H- imidazole-5-methanol; 2-butyl-4-chloro-5-(hydroxymethyl)-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole
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Molecular Type
Small molecule
Disease Hypertension [ICD-11: BA00] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 200-250 mcg/L
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability
Bioavailability
The bioavailability of drug is 33%
Clearance
The renal clearance of drug is 75 mL/min
Clearance
The drug present in the plasma can be removed from the body at the rate of 8.2 mL/min/kg
Elimination
A single oral dose of losartan leads to 4% recovery in the urine as unchanged losartan, 6% in the urine as the active metabolite
Elimination
12% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 1.5 - 2.5 hours
Half-life
The concentration or amount of drug in body reduced by one-half in 1.8 hours
Metabolism
The drug is metabolized via the cytochrome P450s like CYP2C9
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.94873 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 0.01%
Vd
The volume of distribution (Vd) of drug is 34.4 +/- 17.9 L
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.37 L/kg
Water Solubility
The ability of drug to dissolve in water is measured as 0.048 mg/mL
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C22H23ClN6O
PubChem CID
3961
Canonical SMILES
CCCCC1=NC(=C(N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NNN=N4)CO)Cl
InChI
1S/C22H23ClN6O/c1-2-3-8-20-24-21(23)19(14-30)29(20)13-15-9-11-16(12-10-15)17-6-4-5-7-18(17)22-25-27-28-26-22/h4-7,9-12,30H,2-3,8,13-14H2,1H3,(H,25,26,27,28)
InChIKey
PSIFNNKUMBGKDQ-UHFFFAOYSA-N
CAS Number
CAS 114798-26-4
ChEBI ID
CHEBI:6541
TTD Drug ID
D0DD0K
DrugBank ID
DB00678
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Apocynin      Picrorhiza kurrooa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model A 5/6 nephrectomy mouse model of CDK was used in this study.
                    Experimental
                    Result(s)		 Apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.
          L-carnitine      Homo sapiens     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) in rat.
                    Experimental
                    Result(s)		 The combined therapy of losartan and L-carnitine affords additive beneficial effects against diabetes-associated endothelial dysfunction, possibly via normalizing the dysregulated eNOS and reducing the inflammation and oxidative stress in diabetic rats.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Mycophenolate mofetil      Penicillium stoloniferum     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression AGTRAP  Molecule Info 
Pathway MAP
                    In-vivo Model Male Sprague-Dawley rats, weighing 225 to 250 g were used in this study.
                    Experimental
                    Result(s)		 MMF treatment decreases CsA-induced nephrotoxicity, and combined treatment with LSRT has a synergistic effect in preventing chronic CsA nephrotoxicity.
Target and Pathway
Target(s) Angiotensin II receptor type-1 (AGTR1)  Molecule Info  [5]
KEGG Pathway Calcium signaling pathway Click to Show/Hide
2 cGMP-PKG signaling pathway
3 Neuroactive ligand-receptor interaction
4 Adrenergic signaling in cardiomyocytes
5 Vascular smooth muscle contraction
6 Renin-angiotensin system
7 Renin secretion
8 Pathways in cancer
NetPath Pathway TGF_beta_Receptor Signaling Pathway Click to Show/Hide
Panther Pathway Angiotensin II-stimulated signaling through G proteins and beta-arrestin Click to Show/Hide
Pathwhiz Pathway Angiotensin Metabolism Click to Show/Hide
2 Muscle/Heart Contraction
Pathway Interaction Database Arf6 trafficking events Click to Show/Hide
2 Arf6 signaling events
3 Angiopoietin receptor Tie2-mediated signaling
Reactome Peptide ligand-binding receptors Click to Show/Hide
2 G alpha (q) signalling events
WikiPathways ACE Inhibitor Pathway Click to Show/Hide
2 GPCRs, Class A Rhodopsin-like
3 Gastrin-CREB signalling pathway via PKC and MAPK
4 Peptide GPCRs
5 Allograft Rejection
6 GPCR ligand binding
7 GPCR downstream signaling
References
Reference 1 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: 590).
Reference 2 Apocynin combined with drugs as coadjuvant could be employed to prevent and/or treat the chronic kidney disease. Ren Fail. 2018 Nov;40(1):92-98.
Reference 3 Combination therapy with losartan and L-carnitine protects against endothelial dysfunction of streptozotocin-induced diabetic rats. Eur J Pharmacol. 2014 Dec 5;744:10-7.
Reference 4 Synergistic effects of mycophenolate mofetil and losartan in a model of chronic cyclosporine nephropathy. Transplantation. 2003 Feb 15;75(3):309-15.
Reference 5 Radioligand binding assays: application of [(125)I]angiotensin II receptor binding. Methods Mol Biol. 2009;552:131-41.
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