Clascoterone is a topical androgen receptor inhibitor used for the treatment of acne vulgaris and under investigation for androgenic alopecia. It works by competitively blocking dihydrotestosterone (DHT) at the androgen receptor in the skin, reducing sebum production and inflammation. Unlike systemic antiandrogens, clascoterone acts locally, with minimal systemic absorption, making it a safer option for long-term dermatological use.
It is marketed under the brand name Winlevi® as a topical cream formulation (1%).
Therapeutic indications include:
• Acne vulgaris in patients aged 12 years and older
• Under investigation for androgenetic alopecia (male and female pattern hair loss)
Parent: Clascoterone
Impurities in clascoterone arise from its multi-step steroidal synthesis, which involves modifications of the progesterone backbone, including halogenation, esterification, and enone formation. Due to its steroidal structure, impurities from degradation (especially hydrolysis and oxidation) must also be tightly controlled, following ICH Q3A/B and applicable USP/EP guidelines.
Process-Related Impurities
• Starting materials such as cortexolone (11-deoxycortisol) or related steroid precursors
• Incomplete esterification intermediates
• Over-acylated or under-acylated steroidal by-products
• Residual solvents such as ethyl acetate, methylene chloride, or ethanol
• By-products from base- or acid-catalyzed steps (e.g., keto-isomers)
Degradation Impurities
• Hydrolysis of the butyrate ester to release cortexolone
• Oxidation of the 3-keto or Δ⁴-enone system
• Isomerization of the double bond (Δ⁴ to Δ⁵)
• Photodegradation under UV exposure
Elemental Impurities
• Trace metals like iron, zinc, or palladium (if used in catalysts or equipment)
• Controlled under ICH Q3D for topical drug products
Analytical Techniques for Impurity Detection
Clascoterone is approved for treating acne by reducing sebum production and inflammation through androgen receptor inhibition.
It blocks DHT binding to androgen receptors in the skin, preventing the hormonal stimulation of sebaceous glands.
Very minimally. It is designed for local action with negligible systemic hormonal effects, making it safe for long-term topical use.
Store at 20–25°C (68–77°F), protected from excessive heat and light. Keep the tube tightly closed after each use.
