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| Name | Telmisartan | |||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00966 (APRD01247) | |||||||||||||||||||||||||||||||||||||||
| Type | small molecule | |||||||||||||||||||||||||||||||||||||||
| Groups | approved | |||||||||||||||||||||||||||||||||||||||
| Description | Telmisartan is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. Generally, angiotensin II receptor blockers (ARBs) such as telmisartan bind to the angiotensin II type 1 (AT1) receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure. Recent studies suggest that telmisartan may also have PPAR-gamma agonistic properties that could potentially confer beneficial metabolic effects. |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| CAS number | 144701-48-4 | |||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 514.6169 Monoisotopic: 514.236876224 |
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| Chemical Formula | C33H30N4O2 | |||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=RMMXLENWKUUMAY-UHFFFAOYSA-N | |||||||||||||||||||||||||||||||||||||||
| InChI |
InChI=1S/C33H30N4O2/c1-4-9-30-35-31-21(2)18-24(32-34-27-12-7-8-13-28(27)36(32)3)19-29(31)37(30)20-22-14-16-23(17-15-22)25-10-5-6-11-26(25)33(38)39/h5-8,10-19H,4,9,20H2,1-3H3,(H,38,39)
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| IUPAC Name |
2-(4-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid
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| SMILES |
CCCC1=NC2=C(C=C(C=C2C)C2=NC3=C(C=CC=C3)N2C)N1CC1=CC=C(C=C1)C1=C(C=CC=C1)C(O)=O
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| Mass Spec | Not Available | |||||||||||||||||||||||||||||||||||||||
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| Kingdom | Organic | |||||||||||||||||||||||||||||||||||||||
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| Pharmacology | ||||||||||||||||||||||||||||||||||||||||
| Indication | Used alone or in combination with other classes of antihypertensives for the treatment of hypertension. Also used in the treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes mellitus, as well as the treatment of congestive heart failure (only in patients who cannot tolerate ACE inhibitors). | |||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT1 receptor subtype. It has the highest affinity for the AT1 receptor among commercially available ARBS and has minimal affinity for the AT2 receptor. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II. | |||||||||||||||||||||||||||||||||||||||
| Mechanism of action | Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT1-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Studies also suggest that telmisartan is a partial agonist of PPARγ, which is an established target for antidiabetic drugs. This suggests that telmisartan can improve carbohydrate and lipid metabolism, as well as control insulin resistance without causing the side effects that are associated with full PPARγ activators. | |||||||||||||||||||||||||||||||||||||||
| Absorption | Absolute bioavailability depends on dosage. Food slightly decreases the bioavailability (a decrease of about 6% is seen when the 40-mg dose is administered with food). | |||||||||||||||||||||||||||||||||||||||
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| Protein binding | Highly bound to plasma proteins (>99.5%), mainly albumin and a1-acid glycoprotein. Binding is not dose-dependent. | |||||||||||||||||||||||||||||||||||||||
| Metabolism |
Minimally metabolized by conjugation to form a pharmacologically inactive acylglucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan. |
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| Route of elimination | Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively). | |||||||||||||||||||||||||||||||||||||||
| Half life | Bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours. | |||||||||||||||||||||||||||||||||||||||
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| Toxicity | Intravenous LD50 in rats is 150-200 mg/kg in males and 200 to 250 mg/kg in females. Acute oral toxicity is low: no deaths and no changes occurred in rats or dogs at 2000 mg/kg, the highest dose tested. Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. | |||||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | |||||||||||||||||||||||||||||||||||||||
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| Properties | ||||||||||||||||||||||||||||||||||||||||
| State | solid | |||||||||||||||||||||||||||||||||||||||
| Melting point | 261-263oC | |||||||||||||||||||||||||||||||||||||||
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| PDB Entries | Not Available | |||||||||||||||||||||||||||||||||||||||
| FDA label | show (47.4 KB) | |||||||||||||||||||||||||||||||||||||||
| MSDS | show (101 KB) | |||||||||||||||||||||||||||||||||||||||
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| Drug Interactions | Not Available | |||||||||||||||||||||||||||||||||||||||
| Food Interactions | Not Available | |||||||||||||||||||||||||||||||||||||||
| Targets |
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1. Type-1 angiotensin II receptor Pharmacological action: yesActions: antagonist Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system Organism class: humanUniProt ID: P30556 ![]() Gene: AGTR1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. Peroxisome proliferator-activated receptor gamma Pharmacological action: yesActions: partial agonist Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis Organism class: humanUniProt ID: P37231 ![]() Gene: PPARG ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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Actions: inhibitor
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine UniProt ID: P33261![]() Gene: CYP2C19 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Transporters |
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1. Multidrug resistance protein 1 Actions: inhibitorEnergy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183![]() Gene: ABCB1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. Canalicular multispecific organic anion transporter 1 Actions: inhibitorMediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter UniProt ID: Q92887![]() Gene: ABCC2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. ATP-binding cassette sub-family G member 2 Actions: inhibitorXenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123 UniProt ID: Q9UNQ0![]() Gene: ABCG2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Comments |
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This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.