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| Name | Irbesartan | ||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB01029 (APRD00413) | ||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||||||||
| Description | Irbesartan is an angiotensin receptor blocker (ARB) used mainly for the treatment of hypertension. It competes with angiotensin II for binding at the AT1 receptor subtype. Unlike ACE inhibitors, ARBs do not have the adverse effect of dry cough. The use of ARBs is pending revision due to findings from several clinical trials suggesting that this class of drugs may be associated with a small increased risk of cancer. |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Synonyms | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Salts | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 138402-11-6 | ||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 428.5294 Monoisotopic: 428.232459548 |
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| Chemical Formula | C25H28N6O | ||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=YOSHYTLCDANDAN-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||||||||
| InChI |
InChI=1S/C25H28N6O/c1-2-3-10-22-26-25(15-6-7-16-25)24(32)31(22)17-18-11-13-19(14-12-18)20-8-4-5-9-21(20)23-27-29-30-28-23/h4-5,8-9,11-14H,2-3,6-7,10,15-17H2,1H3,(H,27,28,29,30)
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| IUPAC Name |
2-butyl-3-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1,3-diazaspiro[4.4]non-1-en-4-one
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| SMILES |
CCCCC1=NC2(CCCC2)C(=O)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1
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| Mass Spec | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||||||||
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| Pharmacology | |||||||||||||||||||||||||||||||||||||||||||
| Indication | For the treatment of hypertension, as well as diabetic nephropathy with an elevated serum creatinine and proteinuria (>300 mg/day) in patients with type 2 diabetes and hypertension. Irbesartan is also used as a second line agent in the treatment of congestive heart failure. | ||||||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Angiotensin II, the principal pressor agent of the renin-angiotensin system, is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Irbesartan is a specific competitive antagonist of AT1 receptors with a much greater affinity (more than 8500-fold) for the AT1 receptor than for the AT2 receptor and no agonist activity. Irbesartan's inhibition of angiotensin II binding to the AT1 receptor leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure. | ||||||||||||||||||||||||||||||||||||||||||
| Mechanism of action | Irbesartan is a nonpeptide tetrazole derivative and an angiotensin II antagonist that selectively blocks the binding of angiotensin II to the AT1 receptor. In the renin-angiotensin system, angiotensin I is converted by angiotensin-converting enzyme (ACE) to form angiotensin II. Angiotensin II stimulates the adrenal cortex to synthesize and secrete aldosterone, which decreases the excretion of sodium and increases the excretion of potassium. Angiotensin II also acts as a vasoconstrictor in vascular smooth muscle. Irbesartan, by blocking the binding of angiotensin II to the AT1 receptor, promotes vasodilation and decreases the effects of aldosterone. The negative feedback regulation of angiotensin II on renin secretion is also inhibited, but the resulting rise in plasma renin concentrations and consequent rise in angiotensin II plasma concentrations do not counteract the blood pressure–lowering effect that occurs. The action of ARBs is different from ACE inhibitors, which block the conversion of angiotensin I to angiotensin II, meaning that the production of angiotensin II is not completely inhibited, as the hormone can be formed via other enzymes. Also, unlike ACE inhibitors, irbesartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough). | ||||||||||||||||||||||||||||||||||||||||||
| Absorption | Rapid and complete with an average absolute bioavailability of 60-80%. Food has no affect on bioavailability. | ||||||||||||||||||||||||||||||||||||||||||
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| Protein binding | 90% bound to serum proteins (primarily albumin and a1-acid glycoprotein) with negligible binding to cellular components of blood. | ||||||||||||||||||||||||||||||||||||||||||
| Metabolism | Hepatic. Irbesartan is metabolized via glucuronide conjugation and oxidation. In vitro studies of irbesartan oxidation by cytochrome P450 isoenzymes indicated irbesartan was oxidized primarily by 2C9; metabolism by 3A4 was negligible. | ||||||||||||||||||||||||||||||||||||||||||
| Route of elimination | Irbesartan is metabolized via glucuronide conjugation and oxidation. Irbesartan and its metabolites are excreted by both biliary and renal routes. Irbesartan is excreted in the milk of lactating rats. | ||||||||||||||||||||||||||||||||||||||||||
| Half life | 11-15 hours | ||||||||||||||||||||||||||||||||||||||||||
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| Toxicity | Hypotension and tachycardia; bradycardia might also occur from overdose, LD50=mg/kg(orally in rat) | ||||||||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Properties | |||||||||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||||||||
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| FDA label | show (263 KB) | ||||||||||||||||||||||||||||||||||||||||||
| MSDS | show (57.3 KB) | ||||||||||||||||||||||||||||||||||||||||||
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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:
Pharmacological action: unknown
Actions: other/unknown Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3' Organism class: humanUniProt ID: P05412 ![]() Gene: JUN ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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Actions: substrate, inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol) UniProt ID: P10632![]() Gene: CYP2C8 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate, inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan UniProt ID: P11712![]() Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. UDP-glucuronosyltransferase 1-3 Actions: substrateUDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds UniProt ID: P35503![]() Gene: UGT1A3 ![]() Protein Sequence: FASTA SNPs: SNPJam Report ![]() References:
4. Prostaglandin G/H synthase 1 Actions: substrateMay play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells UniProt ID: P23219![]() Gene: PTGS1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177![]() Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants UniProt ID: P10635![]() Gene: CYP2D6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684![]() Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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