Relugolix is a synthetic, non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist used as an active pharmaceutical ingredient in hormone-dependent disorders. It is marketed as ORGOVYX for advanced prostate cancer and is also used in combination products such as MYFEMBREE for uterine fibroids and endometriosis.
Relugolix is a small-molecule, anhydrous crystalline free base with the molecular formula C29H27F2N7O5S and molecular weight 623.63 g/mol. FDA describes it as a white to off-white to slightly yellow solid with low aqueous solubility.
Relugolix, also known as TAK-385 and RVT-601, competitively binds to pituitary GnRH receptors. This suppresses the release of luteinizing hormone and follicle-stimulating hormone and consequently reduces sex-hormone production.
The pharmaceutical API is the free-base form, not a sodium salt. FDA's chemistry review specifically describes relugolix as an anhydrous crystalline free base.
| Parameter | Value |
|---|---|
| Chemical Name | N-(4-{1-[(2,6-difluorophenyl)methyl]-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl}phenyl)-N′-methoxyurea |
| CAS Number | 737789-87-6 |
| Molecular Formula | C29H27F2N7O5S |
| Molecular Weight | 623.63 g/mol |
| Chemical Type | Non-peptide small molecule |
| Drug Class | GnRH receptor antagonist |
| Physical Form | Anhydrous crystalline free base |
| Appearance | White to off-white to slightly yellow solid |
| Chirality | Achiral |
| Water Solubility | 0.04 mg/mL at 25°C |
| Melting Point | 228°C, decomposition (commercial/reference physical property) |
FDA confirms the formula, molecular weight, solid-state description and water solubility. Its chemistry review also specifically identifies relugolix as an anhydrous crystalline free base without chiral centers.
Relugolix is used as a GnRH receptor antagonist in hormone-dependent conditions.
Its approved applications include:
The FDA-approved ORGOVYX product contains 120 mg relugolix per tablet, while MYFEMBREE contains 40 mg relugolix together with estradiol and norethindrone acetate.
Relugolix drug-substance quality control includes appearance, identification, assay, related substances, water content and microbiological testing. FDA's chemistry review confirms that the proposed drug-substance specification includes UV and HPLC-retention-time identification, assay, related substances, water content and microbiological examination.
Important analytical controls include:
FDA classified relugolix as a BCS-4 drug substance, with low solubility and low permeability.
Relugolix API manufacturing requires careful control of chemical identity, crystalline form, assay, related substances, moisture and residual solvents. Since relugolix is an anhydrous crystalline free base, solid-state consistency is an important aspect of API quality control.
FDA's regulatory chemistry review found the drug substance quality assessment adequate and reported that registration and clinical batches conformed to the proposed specifications with low impurity levels.
Relugolix API should be stored in appropriately sealed pharmaceutical packaging under controlled environmental conditions. Commercial reference material is commonly stored under controlled low-temperature conditions, while the FDA-approved finished ORGOVYX tablets are stored at or below 30°C. The finished-product storage condition should not automatically be treated as the API storage specification.
Typical Relugolix API documentation may include:
Relugolix is a commercially established GnRH receptor antagonist with clearly defined chemical identity and regulatory quality requirements. A reliable Relugolix API quality program should control assay, related substances, moisture, residual solvents and solid-state characteristics using validated analytical methods.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Heavy Metals | NMT 20 ppm |
| Individual Impurity | NMT 0.20% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 1.0% |