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| Name | Exemestane | ||||||||||||||||||||||||||||||||||||
| Accession Number | DB00990 (APRD00144) | ||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||
| Description | Exemestane is an oral steroidal aromatase inhibitor used in the adjuvant treatment of hormonally-responsive (also called hormone-receptor-positive, estrogen-responsive) breast cancer in postmenopausal women. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation. |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Synonyms |
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| Brand name mixtures | Not Available | ||||||||||||||||||||||||||||||||||||
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| CAS number | 107868-30-4 | ||||||||||||||||||||||||||||||||||||
| Weight |
Average: 296.4034 Monoisotopic: 296.177630012 |
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| Chemical Formula | C20H24O2 | ||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=BFYIZQONLCFLEV-DAELLWKTSA-N | ||||||||||||||||||||||||||||||||||||
| InChI |
InChI=1S/C20H24O2/c1-12-10-14-15-4-5-18(22)20(15,3)9-7-16(14)19(2)8-6-13(21)11-17(12)19/h6,8,11,14-16H,1,4-5,7,9-10H2,2-3H3/t14-,15-,16-,19+,20-/m0/s1
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| IUPAC Name |
(1S,2R,10R,11S,15S)-2,15-dimethyl-8-methylidenetetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-diene-5,14-dione
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| SMILES |
[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC(=C)C2=CC(=O)C=C[C@]12C
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| Mass Spec | Not Available | ||||||||||||||||||||||||||||||||||||
| Taxonomy | |||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||
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| Pharmacology | |||||||||||||||||||||||||||||||||||||
| Indication | For the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy. | ||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Aromatase is an enzyme that converts hormones to estrogen in the body's adrenal glands. The aromatase inhibitors (AIs) are drugs that reduce estrogen levels by blocking the action of aromatase in the adrenal glands. The selective AIs (SAIs) selectively reduce levels of estrogen without interfering with levels of other steroid hormones that are produced by the adrenal gland. Drugs in this class include anastrozole (Arimidex ™), letrozole (Femara ™) and exemestane (Aromasin ™). | ||||||||||||||||||||||||||||||||||||
| Mechanism of action | Breast cancer cell growth may be estrogen-dependent. Aromatase (exemestane) is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer. Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as "suicide inhibition". Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on the adrenal biosynthesis of corticosteroids or aldosterone. This reduction in serum and tumor concentrations of estrogen delays tumor growth and disease progression. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme. | ||||||||||||||||||||||||||||||||||||
| Absorption | 42% | ||||||||||||||||||||||||||||||||||||
| Volume of distribution | Not Available | ||||||||||||||||||||||||||||||||||||
| Protein binding | 90% (mainly α1-acid glycoprotein and albumin) | ||||||||||||||||||||||||||||||||||||
| Metabolism |
Hepatic |
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| Route of elimination | Not Available | ||||||||||||||||||||||||||||||||||||
| Half life | 24 hours | ||||||||||||||||||||||||||||||||||||
| Clearance | Not Available | ||||||||||||||||||||||||||||||||||||
| Toxicity | Convulsions | ||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | ||||||||||||||||||||||||||||||||||||
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| Properties | |||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||
| Melting point | 155.13oC | ||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||
| General Reference |
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| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||
| FDA label | show (74.6 KB) | ||||||||||||||||||||||||||||||||||||
| MSDS | Not Available | ||||||||||||||||||||||||||||||||||||
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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:
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| Enzymes |
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Actions: substrate
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: inhibitor
Catalyzes the formation of aromatic C18 estrogens from C19 androgens UniProt ID: P11511![]() Gene: CYP19A1 ![]() 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.