Clascoterone Chemical Properties

Boiling point:

538.9±50.0 °C(Predicted)

Density 

1.19

storage temp. 

Store at -20°C

solubility 

Soluble in DMSO

form 

Powder

pka

12.98±0.10(Predicted)

InChIKey

GPNHMOZDMYNCPO-PDUMRIMRSA-N

SMILES

C1(=O)C=C2[C@](C)(CC1)[C@]1([H])[C@]([H])([C@@]3([H])[C@@](CC1)(C)[C@@](OC(=O)CC)(C(=O)CO)CC3)CC2

Clascoterone Usage And Synthesis

Description

Clascoterone (Winlevi®) is an androgen receptor inhibitor being developed as a topical cream and solution by Cassiopea (a spin-out company of Cosmo Pharmaceuticals) for the treatment of androgen-dependent skin disorders, including androgenetic alopecia and acne vulgaris. Although the exact mechanism of action of clascoterone for the topical treatment of acne vulgaris is unknown, the drug is believed to compete with the androgen dihydrotestosterone for binding to androgen receptors in the sebaceous gland and hair follicles to attenuate signalling necessary for acne pathogenesis. In August 2020, clascoterone cream 1% received its first approval in the USA for the topical treatment of acne vulgaris in patients 12 years of age or older. Clinical studies of a different formulation of clascoterone (a solution containing a higher concentration of the drug) for the treatment of androgenetic alopecia are underway in Germany and the USA. This article summarizes the milestones in the development of clascoterone leading to this first approval for the topical treatment of acne vulgaris.

Chemical Properties

Clascoterone is a white to almost white powder, practically insoluble in water. The compound has the empirical formula C24H34O5 andmolecular weight of 402.5 g/mol.

Uses

Clascoterone (cortexolone 17α-propionate, CB-03-01) is a novel antagonist of androgen receptors. It binds to androgen receptors with high affinity. By competing with androgens for binding to androgen receptors, clascoterone works by blocking the androgen receptor signalling cascades that promote acne pathogenesis, such as sebaceous gland proliferation, excess sebum production, and inflammatory pathways. In August 2020, FDA approved clascoterone for the first-in-class topical treatment of acne (acne vulgaris) in male and female patients 12 years and older. Clascoterone is also being investigated as a novel treatment for androgenetic alopecia.

Uses

Clascoterone is being developed as a topical cream by Cassiopea for androgen-?dependent skin disorders.

Biological Activity

Clascoterone is a high-affinity androgen receptor (AR) antagonist (antiandrogen) that antagonizes testosterone-stimulated transcription activity (in reporter cells) as well as DHT-induced production of lipids and inflammatory cytokines (in human sebocytes) in cultures. When applied topically, clascoterone is as active as cyproterone acetate, and 2-, 3-, and 4-times, respectively, more active than finasteride, flutamide, and progesterone in vivo (local antiandrogenic activity in hamster′s flank organ; 100-400 μg/50 μL acetone/animal).

Side effects

Clascoterone topical application may cause serious side effects: severe itching, burning, peeling, or redness of treated skin; high blood potassium--nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement; or decreased adrenal gland hormones--nausea, vomiting, stomach pain, loss of appetite, feeling tired or light-headed, muscle or joint pain, skin discoloration, craving salty foods.

Safety

Clascoterone(Winlevi) is the only topical acne product with a warning about hypothalamic-pituitary-adrenal (HPA) axis suppression. This may result when Winlevi is used over large surface areas or if use is prolonged. In addition, pediatric patients may be more susceptible. This adverse event was not observed in the pivotal studies or in the long-term open-label extension study. However, it was observed in a small group of patients on Day 14 in a pharmacokinetic study. Normal HPA axis function was observed at follow-up at 4 weeks after end of treatment.

Mode of action

Clascoterone is an androgen receptor inhibitor. The mechanism of action of WINLEVI cream for the topical treatment of acne vulgaris is unknown.

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