CB-03-01
[CAS# 19608-29-8]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs
• Name: CB-03-01
• Synonyms: 21-Hydroxy-17-(1-oxopropoxy)pregn-4-ene-3,20-dione
• Molecular Formula: C₂₄H₃₄O₅
• Molecular Weight: 402.52
• CAS Registry Number: 19608-29-8
• EC Number: 685-282-9
• SMILES: CCC(=O)O[C@@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C)C(=O)CO

Properties

• Solubility: 10 mM (DMSO) (Expl.)
• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.555, Calc.^*
• Boiling Point: 538.9±50.0 °C (760 mmHg), Calc.^*
• Flash Point: 179.3±23.6 °C, Calc.^*

Safety Data

• Hazard Symbols: GHS08 Warning
• Risk Statements: H341
• Safety Statements: P203-P280-P318-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Germ cell mutagenicity	Muta.	2	H341

Discovery and Applications

CB-03-01, also known as cortexolone 17α-propionate, is a synthetic derivative of 11-deoxycortisol. It has gained significant attention as a promising topical antiandrogen and anti-inflammatory agent. Unlike traditional systemic antiandrogens, CB-03-01 is designed to exert its effects locally, reducing potential systemic side effects and enhancing its suitability for dermatological applications.

The discovery of CB-03-01 was rooted in the need for novel treatments targeting androgen-mediated disorders, particularly acne and androgenetic alopecia. Researchers aimed to develop a compound that could selectively inhibit the effects of dihydrotestosterone (DHT) at the skin level without altering systemic hormone levels. The introduction of the propionate ester at the 17α-position significantly enhanced its stability and skin penetration while maintaining high specificity for androgen receptors.

CB-03-01 acts by competitively antagonizing androgen receptors in the skin, thereby preventing DHT from binding and activating these receptors. This mechanism is crucial for reducing sebum production, a major contributing factor in acne pathogenesis. Additionally, the compound exhibits potent anti-inflammatory properties, making it effective in controlling the inflammatory lesions associated with acne vulgaris.

One of the most significant clinical advancements of CB-03-01 is its development as a topical formulation under the trade name clascoterone. Clinical trials have demonstrated its efficacy in significantly reducing both inflammatory and non-inflammatory acne lesions with minimal irritation or adverse effects. Its unique pharmacological profile has also sparked interest in its potential application for treating androgenetic alopecia, hirsutism, and other skin conditions influenced by androgen activity.

The synthesis of CB-03-01 involves selective chemical modifications of 11-deoxycortisol, emphasizing the introduction of the propionate ester. The resulting compound displays enhanced lipophilicity, facilitating its absorption into the sebaceous glands where it exerts its therapeutic effects. This innovative approach has marked a departure from traditional systemic therapies, offering a targeted solution for skin-specific conditions.

Future research directions include exploring the long-term safety profile of CB-03-01, optimizing its formulation for broader dermatological applications, and investigating its efficacy in combination with other therapies. Advances in understanding its molecular interactions could also pave the way for the design of next-generation topical antiandrogens.

References

2024. Integrated Short-Term and Long-Term Efficacy of Topical Clascoterone Cream 1% in Patients Aged 12 Years or Older With Acne Vulgaris. Journal of drugs in dermatology : JDD, 23(12).
DOI: 10.36849/jdd.7719

2024. Comparison of the Efficacy of Clascoterone, Trifarotene, and Tazarotene for the Treatment of Acne: A Systematic Literature Review and Meta-Analysis. Dermatology and Therapy, 14(5).
DOI: 10.1007/s13555-024-01175-3

2023. TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Research, 52(D1).
DOI: 10.1093/nar/gkad751