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| Name | Aminoglutethimide | ||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00357 (APRD00592) | ||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||||||||
| Description | An aromatase inhibitor that produces a state of “medical” adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454) |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Synonyms |
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| Salts | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Brand mixtures | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 125-84-8 | ||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 232.2783 Monoisotopic: 232.121177766 |
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| Chemical Formula | C13H16N2O2 | ||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=ROBVIMPUHSLWNV-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||||||||
| InChI |
InChI=1S/C13H16N2O2/c1-2-13(8-7-11(16)15-12(13)17)9-3-5-10(14)6-4-9/h3-6H,2,7-8,14H2,1H3,(H,15,16,17)
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| IUPAC Name |
3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione
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| SMILES |
CCC1(CCC(=O)NC1=O)C1=CC=C(N)C=C1
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| Mass Spec | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Taxonomy | |||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||||||||
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| Substructures |
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| Pharmacology | |||||||||||||||||||||||||||||||||||||||||||
| Indication | For the suppression of adrenal function in selected patients with Cushing's syndrome, malignant neoplasm of the female breast, and carcinoma in situ of the breast. | ||||||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Aminoglutethimide inhibits the enzymatic conversion of cholesterol to D5-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens. | ||||||||||||||||||||||||||||||||||||||||||
| Mechanism of action | Aminoglutethimide reduces the production of D5-pregnenolone and blocks several other steps in steroid synthesis, including the C-11, C-18, and C-21 hydroxylations and the hydroxylations required for the aromatization of androgens to estrogens, mediated through the binding of aminoglutethimide to cytochrome P-450 complexes. Specifically, the drug binds to and inhibits aromatase which is essential for the generation of estrogens from androstenedione and testosterone. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide. The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since aminoglutethimide increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement. Although aminoglutethimide inhibits the synthesis of thyroxine by the thyroid gland, the compensatory increase in thyroid-stimulating hormone (TSH) is frequently of sufficient magnitude to overcome the inhibition of thyroid synthesis due to aminoglutethimide. In spite of an increase in TSH, aminoglutethimide has not been associated with increased prolactin secretion. | ||||||||||||||||||||||||||||||||||||||||||
| Absorption | Rapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution. | ||||||||||||||||||||||||||||||||||||||||||
| Volume of distribution | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Protein binding | 21-25% | ||||||||||||||||||||||||||||||||||||||||||
| Metabolism |
Hepatic. 34-54% of the administered dose is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as an N-acetyl derivative.
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| Route of elimination | After ingestion of a single oral dose, 34%-54% is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as the N-acetyl derivative. | ||||||||||||||||||||||||||||||||||||||||||
| Half life | 12.5 ± 1.6 hours | ||||||||||||||||||||||||||||||||||||||||||
| Clearance | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Toxicity | Oral LD50s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50s (mg/kg): rats, 156; dogs, >100. Symptoms of overdose include respiratory depression, hypoventilation, hypotension, hypovolemic shock due to dehydration, somnolence, lethargy, coma, ataxia, dizziness, fatigue, nausea, and vomiting. | ||||||||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Prices | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Patents | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Properties | |||||||||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| General Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| External Links |
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| ATC Codes |
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| AHFS Codes | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| FDA label | show (122 KB) | ||||||||||||||||||||||||||||||||||||||||||
| MSDS | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Interactions | |||||||||||||||||||||||||||||||||||||||||||
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| Targets |
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Pharmacological action: yes
Actions: inhibitor Catalyzes the formation of aromatic C18 estrogens from C19 androgens Organism class: humanUniProt ID: P11511 ![]() Gene: CYP19A1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. Cholesterol side-chain cleavage enzyme, mitochondrial Pharmacological action: unknownActions: inhibitor Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone Organism class: humanUniProt ID: P05108 ![]() Gene: CYP11A1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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Actions: inducer
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:
Actions: inducer
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: inducer
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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