Description
Summary Abstract
Arimistane (androsta-3,5-diene-7,17-dione; CAS 1420-49-1) is a naturally occurring metabolite of dehydroepiandrosterone (DHEA) and a steroidal irreversible (Type I, “suicide”) aromatase inhibitor. It binds the active site of CYP19A1, the cytochrome P450 responsible for converting testosterone and androstenedione to estradiol and estrone, and upon enzymatic processing generates a reactive intermediate that covalently modifies the enzyme — permanently suppressing aromatase activity until new CYP19A1 protein is synthesized. This mechanism mirrors that of exemestane (Aromasin), a clinically approved steroidal aromatase inhibitor, and makes arimistane a well-characterized pharmacological tool for studying estrogen biosynthesis, HPG axis feedback, and androgen-to-estrogen balance in gonadal, adipose, and breast tissue research models. Available as 25 MG capsules (SKU C-004).
Clinical Indications
Arimistane is applied across several endocrinological and oncological research contexts:
- Aromatase pathway characterization: Used as a pharmacological probe to dissect CYP19A1-dependent estrogen synthesis in gonadal, adipose, and peripheral tissue models.
- Androgen/estrogen ratio studies: Applied to acutely suppress E2/E1 production and model the resulting testosterone flux and HPG axis disinhibition in male endocrine models.
- Breast cancer endocrinology: Structural analogue of exemestane; used in mechanistic studies of aromatase inhibition in hormone-receptor–positive tumor models.
Contraindications
- Pregnancy / reproductive models: Irreversible estrogen suppression poses significant developmental and reproductive toxicity risk; absolute contraindication in any pregnancy-related experimental context.
- Bone metabolism studies: Chronic aromatase inhibition may compromise bone mineral density; osteocalcin and bone-turnover markers should be monitored in extended protocols.
- Pediatric models: Estrogen is essential for skeletal maturation and pubertal development; exposure in immature models carries significant endocrine disruption risk.
Mechanism of Action (MOA)
Arimistane permanently suppresses estrogen biosynthesis via an irreversible, covalent mechanism at the aromatase active site:
CYP19A1 Suicide Inhibition
Arimistane is recognized as a substrate by CYP19A1 (aromatase). During enzymatic processing, it generates a reactive intermediate that forms a covalent bond with the enzyme’s heme-containing active site, producing irreversible enzyme inactivation. Restoration of aromatase activity requires de novo protein synthesis, giving the compound prolonged pharmacodynamic duration.
Estrogen Biosynthesis Suppression
By permanently inactivating CYP19A1, arimistane blocks the conversion of testosterone → estradiol (E2) and androstenedione → estrone (E1) in both gonadal and peripheral tissues. Circulating estrogen levels fall sharply, removing estrogenic negative feedback from the hypothalamus and pituitary.
HPG Axis Disinhibition
Reduced E2-mediated negative feedback on hypothalamic GnRH neurons and pituitary gonadotrophs elevates LH and FSH secretion in male models, driving increased intratesticular testosterone production — a pharmacodynamic profile relevant to male HPG axis recovery and testosterone regulation research.
Structural Analogy to Exemestane
As a steroidal (Type I) inhibitor, arimistane’s mechanism contrasts with non-steroidal (Type II) inhibitors such as anastrozole and letrozole, which reversibly chelate the CYP19A1 heme via triazole nitrogens. The steroidal scaffold of arimistane confers high active-site affinity and the capacity for irreversible covalent inactivation — a pharmacological distinction of mechanistic significance in aromatase biology research.
Key Features & Specifications
Arimistane provides a structurally defined, irreversible pharmacological tool for aromatase and estrogen research:
Chemical Analysis
| Property | Specification Reference Data |
|---|---|
| IUPAC Name | (8R,9S,10R,13S,14S)-10,13-dimethyl-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-7,17-dione |
| CAS Number | 1420-49-1 |
| Molecular Formula | C19H24O2 |
| Molecular Weight | 284.39 g/mol |
| PubChem CID | 5311 |
| Synonyms | Androsta-3,5-diene-7,17-dione; Androst-3,5-dien-7,17-dione; NSC 134910; 3-Deoxy-7-oxo-DHEA; 3,5-Androstadiene-7,17-dione |
| Form / Variation | 25 MG Capsules (SKU C-004, $58.00) |
Storage, Safety, and Handling
Storage Protocol
Store at 15–25°C in a sealed, light-protected container away from moisture and oxidizing agents. The conjugated diene-ketone system is susceptible to photodegradation; amber glass packaging is recommended for extended storage. Capsule formulations remain stable at room temperature when sealed. For solution preparation, arimistane dissolves in DMSO or ethanol; aqueous solubility is limited given its lipophilic steroidal scaffold.
Handling & Compliance
Handle with standard PPE (nitrile gloves, eye protection) to avoid inadvertent percutaneous absorption of this potent endocrine-active compound. Arimistane (androsta-3,5-diene-7,17-dione) is listed under World Anti-Doping Agency (WADA) S4 (Hormone and Metabolic Modulators); researchers in sport science settings must document and justify its use. Comply with applicable institutional and jurisdictional regulations governing steroidal research compounds.