1What Is Clascoterone (CB-03-01)?
⚠ Usage Notice: For laboratory research & pharmaceutical formulation raw material only, not for direct human oral/injection use. Clascoterone is a prescription-only API (Rx) in jurisdictions where approved. All handling must comply with applicable institutional and regulatory guidelines.
At a Glance
Clascoterone (development code CB-03-01, INN: Clascoterone), chemically known as cortexolone 17α-propionate, is a steroidal small molecule that functions as a high-affinity, competitive androgen receptor (AR) antagonist with a binding affinity of Ki = 40 nM for the human AR.
Designed as a "soft drug," Clascoterone is engineered for local pharmacological activity in the skin with rapid systemic inactivation. Upon entering the bloodstream, it is immediately hydrolyzed to cortexolone (11-deoxycortisol) — an endogenous, biologically inactive metabolite — achieving the therapeutic ideal of strong local efficacy combined with negligible systemic exposure (Cmax ~4.5 ng/mL after topical application).
Clascoterone is the first and only topical androgen receptor antagonist to receive FDA approval (August 2020, as Winlevi® 1% cream for acne vulgaris in patients ≥12 years). It is also in advanced clinical development (Breezula® topical solution) for androgenetic alopecia (AGA). Supplied as a ≥99% HPLC-verified powder, it is intended for pharmaceutical formulation R&D, bioequivalence testing, dermatological research, and analytical reference standard use.
To appreciate why Clascoterone represents a paradigm shift in topical anti-androgen therapy, it is essential to understand the unmet need it addresses. For decades, the only anti-androgens available for dermatological applications were systemic agents (e.g., spironolactone, finasteride, oral contraceptives) that carried significant endocrine side-effect burdens — from sexual dysfunction and gynecomastia to teratogenicity. Clascoterone's soft drug design fundamentally bypasses this problem: it acts at the site of application as a potent AR blocker, then self-inactivates upon entering systemic circulation, leaving no hormonal footprint.
2Physicochemical Specifications & Identity Data
The following specifications define the identity, purity, and physical characteristics of our Clascoterone CB-03-01 powder. Each batch ships with a Certificate of Analysis (COA) documenting HPLC purity (≥99%), identity confirmation via NMR and HPLC retention-time matching, and residual solvent profiling.
| Technical Specifications — Clascoterone (CB-03-01) | |
|---|---|
| Product Name | Clascoterone (CB-03-01; Cortexolone 17α-propionate) |
| CAS Number | 19608-29-8 |
| Synonyms | Cortexolone 17α-propionate; 21-Hydroxy-17-(1-oxopropoxy)pregn-4-ene-3,20-dione; CB-03-01; C17P |
| Molecular Formula | C24H34O5 |
| Molecular Weight | 402.52 g/mol |
| MDL Number | MFCD18384978 |
| PubChem CID | 11750009 |
| Chemical Class | Steroidal (pregnane derivative) — non-androgenic C4-substituted steroid |
| Appearance | White to off-white / pale beige crystalline powder |
| Purity | ≥99% (HPLC) |
| Solubility (DMSO) | ≥100 mg/mL (248 mM) — freely soluble |
| Solubility (Ethanol / Acetone) | Soluble in organic solvents (typical for steroid core) |
| Melting Point | Not officially published; steroid esters typically 95–130°C |
| Optical Rotation | [α]D consistent with 17α-propionate pregnane stereochemistry |
| Storage Conditions | −20°C, sealed, desiccated, protected from light |
| Shelf Life (Powder) | 36 months at −20°C; 24 months at 2–8°C |
| Shelf Life (In Solution) | 12 months at −80°C; 1 month at −20°C |
| Intended Use | Pharmaceutical R&D, formulation research, analytical reference, bioequivalence studies |
Why 99% purity matters for formulation R&D: Clascoterone is intended for topical pharmaceutical formulations — creams, gels, solutions, and medicated delivery systems. At ≥99% HPLC purity, formulators can rely on accurate dose-potency calculations, minimize unknown impurity-related stability issues during accelerated aging studies, and meet the stringent API purity thresholds required for ANDA (Abbreviated New Drug Application) and 505(b)(2) development pathways. Lower-purity grades (<98%) introduce unnecessary variables that compromise batch-to-batch reproducibility in formulation development.
3Core Advantages & Mechanism of Action
Clascoterone's value proposition rests on three pillars: a validated soft drug design, a well-characterized AR antagonist mechanism, and an FDA-approval precedent that de-risks formulation development. Below we detail each.
3.1 Mechanism of Action: Competitive AR Antagonism at the Sebocyte and Dermal Papilla Level
Clascoterone competes with dihydrotestosterone (DHT) and testosterone for binding to the androgen receptor (AR) in target tissues — primarily sebocytes (sebaceous gland cells) and dermal papilla cells (hair follicle regulatory cells). With a binding affinity of Ki = 40 nM for human AR, Clascoterone effectively displaces endogenous androgens from the receptor. Critically, the Clascoterone-AR complex does not translocate to the nucleus to activate androgen-responsive gene transcription programs, effectively silencing the downstream signaling cascade.
(AR — Sebocyte) → Nuclear Translocation
& Gene Activation
(CB-03-01) → Androgen Receptor
(AR — Occupied) ⊛ No Nuclear Translocation
No Gene Activation
(Lipid Synthesis) + ↓ Inflammatory Cytokines
(IL-6, IL-8, TNF-α) + ↓ Dermal Papilla AR
Signaling
Mechanism: Clascoterone competitively occupies the AR ligand-binding domain, preventing DHT/testosterone from driving downstream gene expression — reducing sebum production, inflammation, and follicular miniaturization signals.
3.2 The Soft Drug Advantage: Local Efficacy, Systemic Safety
Clascoterone is the textbook example of a "soft drug" — a pharmacologically active molecule designed to undergo predictable, rapid metabolic inactivation upon entry into the systemic circulation. Specifically:
- At the application site (skin, hair follicle): Clascoterone remains intact, penetrates the stratum corneum, reaches the sebaceous gland and dermal papilla, and exerts potent AR antagonism locally.
- Upon systemic absorption (via dermal capillaries): Endogenous esterases immediately hydrolyze the 17α-propionate ester, converting Clascoterone to cortexolone (11-deoxycortisol) — an endogenous steroid with no significant AR activity or endocrine effect. Peak plasma levels after topical application are approximately 4.5 ng/mL — orders of magnitude below concentrations required for systemic hormonal perturbation.
This metabolic inactivation mechanism explains why Clascoterone clinical trials reported a systemic adverse event profile comparable to placebo — no sexual dysfunction, no gynecomastia, no menstrual irregularities, and no hypothalamic-pituitary-gonadal (HPG) axis suppression.
3.3 Comparative Potency: Clascoterone vs. Legacy Topical Anti-Androgens
In the hamster flank organ model — a well-established in vivo assay for local anti-androgenic potency — Clascoterone demonstrated the following relative potency ranking (Celasco et al., 2004):
| Compound | Relative Topical Anti-Androgenic Potency | Systemic Safety Profile | FDA-Approved Topical? |
|---|---|---|---|
| Clascoterone (CB-03-01) | Equivalent to Cyproterone Acetate | Soft drug — local only | ✓ Yes (2020) |
| Finasteride | ~0.5× (half as potent locally) | Systemic DHT suppression; sexual AE risk | ✗ No (oral only) |
| Flutamide | ~0.3× | Hepatotoxicity risk; systemic anti-androgen | ✗ No |
| Progesterone | ~0.25× | Hormonal disruption; menstrual effects | ✗ No |
3.4 FDA Approval: De-Risked API for Formulators
Clascoterone's FDA approval (NDA 213433, August 2020) as Winlevi® (clascoterone cream 1%) represents a critical milestone for formulation developers. An FDA-approved API means:
- The active ingredient has passed CMC (Chemistry, Manufacturing & Controls) review, toxicology assessment, and clinical efficacy/safety evaluation
- Reference Listed Drug (RLD) characterization data are publicly available, enabling ANDA/505(b)(2) development with reduced clinical burden
- DMF (Drug Master File) Type II filing pathways are well-established for API sourcing
- Regulatory precedent exists for the excipient compatibility, stability, and delivery profile of topical formulations containing this API
For generic and hybrid-NDA developers, this dramatically lowers the barrier to entry compared to unapproved novel chemical entities.
4Research & Formulation Application Scenarios
Clascoterone is employed across a spectrum of dermatological and pharmaceutical R&D contexts. The following represent the most established and emerging applications.
Acne Vulgaris Formulation Development
Development of generic Winlevi® (clascoterone cream 1%) equivalents, novel cream/gel/lotion formulations, and combination products incorporating clascoterone with other anti-acne actives (retinoids, benzoyl peroxide, antibiotics) for enhanced efficacy.
Androgenetic Alopecia (AGA) Research
Formulation and efficacy testing of clascoterone topical solutions for pattern hair loss. Breezula® Phase 2/3 data demonstrated significant increases in non-vellus target-area hair count vs. placebo.
Bioequivalence Testing & Reference Standard
Use as a certified reference standard for HPLC method development, dissolution testing, impurity profiling, and pharmacokinetic bioequivalence studies supporting ANDA filings.
AR Signaling & Sebocyte Research
In vitro mechanistic studies in human sebocyte and dermal papilla cell cultures investigating androgen-regulated lipid synthesis, inflammatory cytokine production (IL-6, IL-8, TNF-α), and gene expression profiling.
Novel Indication Exploration
Investigational use in hidradenitis suppurativa (HS), seborrheic dermatitis, hirsutism, and other androgen-sensitive dermatological conditions where local AR antagonism may provide therapeutic benefit.
Microneedle & Nanoparticle Delivery R&D
Research into enhanced topical delivery systems — including microneedle patches, lipid nanoparticles, and liposomal encapsulation — for improved follicular targeting and transdermal penetration.
4.1 Formulation Development Considerations
| Key Formulation Parameters for Clascoterone Topicals | |
|---|---|
| Typical Concentration | 1% w/w (FDA-approved); 2.5%–7.5% (Breezula® trials) |
| Compatible Vehicles | O/W creams, hydro-alcoholic gels, non-aqueous solutions, lotions |
| Penetration Enhancers | Ethanol, propylene glycol, dimethyl isosorbide (screen for compatibility) |
| pH Stability Range | pH 4.5–7.0 (ester hydrolysis accelerates at alkaline pH) |
| API Solubilization | Pre-dissolve in ethanol / DMSO before incorporation into aqueous phase |
| Stability Concerns | Hydrolysis of 17α-propionate ester; photodegradation; oxidative degradation |
5Packaging, Storage & Logistics Compliance
Understanding the regulatory classification, shipping requirements, and storage conditions of Clascoterone is critical for procurement, import, and inventory management. This section addresses the most frequent logistical questions.
Packaging
Sealed amber glass vials under nitrogen blanket with tamper-evident caps and moisture-barrier seals. Available in 25 mg, 100 mg, 500 mg, 1 g, 5 g, and bulk configurations.
Storage
Powder: −20°C sealed/dry/dark (36 months) or 2–8°C (24 months). DMSO solution: −80°C (12 months). Avoid moisture, light, repeated freeze-thaw.
Shipping
Ambient or cold-chain (blue ice / −20°C gel packs). Powder is stable for ambient transit ≤10 days. UN: non-regulated for research quantities.
5.1 Is Clascoterone a Controlled or Prohibited Substance?
No. Clascoterone (CAS 19608-29-8) is not listed on any narcotics, psychotropic, or precursor control schedule under the UN Single Convention, the US Controlled Substances Act (21 CFR 1308), or EU drug control frameworks. It is an FDA-approved prescription drug active ingredient (Rx) — which means it is regulated as a pharmaceutical API, not as a controlled substance.
Regulatory Note — Rx Status: While Clascoterone is not a controlled substance, it is the active ingredient in an FDA-approved prescription drug (Winlevi®). In some jurisdictions, APIs for approved drugs may be subject to prescription-only import/export requirements. Buyers should verify their national pharmaceutical import regulations. Clascoterone is not on the WADA Prohibited List (no systemic effect at therapeutic doses).
5.2 Shipping Conditions & Transport Requirements
- Powder form: Ships at ambient temperature with desiccant for standard transit times ≤7–10 days. Cold-chain (blue ice or −20°C gel packs) available upon request and recommended for tropical-climate destinations or extended transit times.
- Pre-dissolved stocks: Ship on dry ice (−78°C) per UN 1845 dangerous goods protocol for Class 9 dry ice shipments.
- UN Hazard Classification: Non-regulated chemical for research quantities (<1 kg). SDS available on request for customs clearance and institutional safety review.
- HS Code: Typically classified under 2937.29 (steroidal hormones / derivatives) — exact code may vary by jurisdiction. Commercial invoice with accurate HS code included in all shipments.
- Import / Customs: As an FDA-approved Rx API, some countries may request an End-Use Declaration or institutional purchase order confirming research/pharmaceutical R&D intent. No DEA import permit is required for the US (non-controlled). EU buyers: verify with national competent authorities for any API-specific import requirements.
- Documentation included: Certificate of Analysis (COA), Safety Data Sheet (SDS), packing list, commercial invoice, and air waybill. Additional documentation (GMP certificate, DMF Letter of Authorization, technical data package) available for qualified pharmaceutical development partners.
5.3 Storage & Shelf Life Summary
| Storage Matrix — Clascoterone Stability | ||
|---|---|---|
| Form & Container | Temperature | Stability Period |
| Solid powder (sealed amber vial, N2 blanket, desiccated) | −20°C | 36 months |
| Solid powder (sealed, desiccated) | 2–8°C | 24 months |
| DMSO stock solution (aliquoted, sealed) | −80°C | 12 months |
| DMSO stock solution (aliquoted, sealed) | −20°C | 1 month |
| Working dilutions (formulation matrix) | Room temp / 4°C | Prepare daily (ester labile) |
To preserve API integrity, avoid repeated freeze-thaw cycles of stock solutions. We recommend single-use aliquoting upon first dissolution. Allow the sealed powder vial to equilibrate to room temperature before opening (prevents moisture condensation). The 17α-propionate ester is susceptible to hydrolysis at elevated pH and temperature — always prepare working solutions fresh and neutralize any basic excipients before incorporating Clascoterone.
6Frequently Asked Questions (FAQ)
Below we address the most common questions from procurement teams, formulators, and researchers evaluating Clascoterone for their programs.
Q: What is the difference between Clascoterone, CB-03-01, and Cortexolone 17α-propionate?
They are the same chemical entity. "Clascoterone" is the INN (International Nonproprietary Name) assigned by WHO. "CB-03-01" is the original development code used by Cassiopea S.p.A. (now Cosmo Pharmaceuticals). "Cortexolone 17α-propionate" (or "C17P") is the systematic chemical name. All refer to CAS 19608-29-8 with molecular formula C24H34O5.
Q: What does "soft drug" mean in the context of Clascoterone?
A "soft drug" is a pharmacologically active compound specifically engineered to undergo rapid, predictable metabolic inactivation upon entering systemic circulation. For Clascoterone, endogenous esterases in the blood hydrolyze the 17α-propionate ester, converting it to cortexolone — an inactive endogenous steroid. This design achieves the ideal of strong local activity (blocking AR in the skin) with negligible systemic endocrine effects.
Q: Is Clascoterone the same as Winlevi® or Breezula®?
No. Winlevi® (clascoterone cream 1%) and Breezula® (clascoterone topical solution) are finished drug products containing Clascoterone as the API, formulated with proprietary excipient blends. Our Clascoterone powder is the pure active pharmaceutical ingredient (API) — a raw material suitable for generic formulation development, bioequivalence testing, and analytical method development. It is not a finished dosage form.
Q: What is the binding affinity (Ki) of Clascoterone for the androgen receptor?
Clascoterone binds to human AR with a Ki (inhibition constant) of 40 nM, as determined by competitive displacement of [3H]methyltrienolone (a synthetic AR ligand) in human prostate cancer cell lysates (GtoPdb/ChEMBL). This places its affinity in the range of potent steroidal anti-androgens, consistent with its demonstrated clinical efficacy at 1% topical concentration.
Q: Can Clascoterone be used orally or by injection?
No. By design, Clascoterone is not orally bioavailable (the 17α-propionate ester is rapidly hydrolyzed in plasma) and not intended for injection. It is designed exclusively for topical application. Systemic administration would result in immediate inactivation to cortexolone and loss of pharmacological activity. Any research use should be confined to topical/transdermal models.
Q: Is Clascoterone a controlled substance?
No. Clascoterone is not a narcotic, psychotropic, or scheduled substance under the UN drug control conventions, US Controlled Substances Act, or any major national drug control framework. It is an FDA-approved prescription API. It is not on the WADA Prohibited List. However, as an Rx drug API, certain jurisdictions may require an End-Use Declaration for import.
Q: What purity grade should I specify for formulation development vs. analytical reference?
For pharmaceutical formulation R&D (generic development): ≥99% HPLC with full impurity profiling, residual solvent certification, and heavy metal analysis. For analytical reference standard use: ≥99.5% HPLC with quantitative NMR purity certification. Our standard supply is ≥99% HPLC; higher-purity reference-grade material with enhanced documentation is available upon request for ANDA-supporting analytical work.
Q: What clinical evidence supports Clascoterone's efficacy?
Two pivotal Phase 3 trials (NCT02608450, NCT02608476) enrolled 1,440 patients and demonstrated that clascoterone cream 1% achieved statistically significant reductions in both inflammatory and non-inflammatory acne lesions after 12 weeks, with a safety profile comparable to placebo (no treatment-related serious adverse events). Additionally, the Breezula® Phase 2 dose-ranging trial (NCT02279823) showed significant increases in target-area non-vellus hair count with a 7.5% BID topical solution in men with AGA.
Q: How does Clascoterone compare to finasteride or spironolactone for research purposes?
Clascoterone differs fundamentally: it is a topical AR antagonist (blocks DHT at the receptor) with soft drug design, while finasteride is a systemic 5α-reductase inhibitor (lowers DHT production) and spironolactone is a systemic AR antagonist with mineralocorticoid activity. For dermatological research requiring local AR blockade without systemic hormonal effects, Clascoterone is the most mechanistically appropriate tool compound currently available as a pure API.
Q: Is the 17α-propionate ester bond stable in formulation?
The ester is stable in anhydrous and slightly acidic (pH 4.5–6.0) environments but undergoes base-catalyzed hydrolysis at pH >7.5. Formulators should avoid highly alkaline excipients, conduct forced-degradation studies (acid/base/oxidative/thermal/photolytic) as part of ICH Q1A stability testing, and monitor cortexolone (des-ester) levels as the primary degradation product during accelerated and long-term stability studies.
Q: Do you provide DMF support for ANDA/505(b)(2) filers?
Yes. For qualified pharmaceutical development partners, we can provide a Type II Drug Master File (DMF) Letter of Authorization (LoA) enabling cross-reference in your ANDA or 505(b)(2) submission, along with enhanced analytical data packages, impurity characterization, and CMC documentation. Contact our technical team to discuss your regulatory filing requirements.
Q: What documentation accompanies a standard order?
Every order includes a Certificate of Analysis (COA) documenting HPLC purity (≥99%), identity confirmation (NMR and HPLC retention time), residual solvent content, and water content (Karl Fischer). A Safety Data Sheet (SDS) is provided. Enhanced documentation — including TGA, DSC, XRD, elemental analysis, and detailed impurity profiling reports — is available for pharmaceutical development accounts.
7Summary & Procurement
Clascoterone (CB-03-01; cortexolone 17α-propionate) represents a landmark in topical anti-androgen therapy — the first and only FDA-approved topical AR antagonist, backed by robust Phase 3 clinical data, a validated soft drug design, and clear regulatory precedent. For pharmaceutical R&D teams, it offers:
- Mechanistic clarity: Competitive AR antagonist with Ki = 40 nM, confirmed by well-characterized in vitro and in vivo pharmacology
- Safety by design: Soft drug metabolism to inactive cortexolone eliminates systemic endocrine risk
- Regulatory precedent: FDA-approved API with published RLD characterization data enabling ANDA/505(b)(2) development
- Broad applicability: Acne, androgenetic alopecia, and emerging dermatological indications with AR-driven pathophysiology
- Formulation flexibility: Compatible with creams, gels, solutions, and advanced delivery systems (microneedles, nanoparticles)
≥99% HPLC Purity
Batch-specific COA with identity, purity, residual solvents, and water content. Reference-grade material available for ANDA analytical work.
DMF & Regulatory Support
Type II DMF LoA and CMC documentation available for qualified pharmaceutical development partners pursuing ANDA/505(b)(2) filings.
Global Shipping & Compliance
Non-controlled substance. Ambient or cold-chain shipping with full customs documentation. End-use declarations supported where required.
Formulation Technical Support
Pre-formulation compatibility guidance, forced degradation study support, impurity reference standards, and analytical method consultation.
Source Clascoterone CB-03-01 ≥99% HPLC Powder for Your R&D Program
Pharmaceutical-grade API with full COA, DMF support, and competitive pricing for R&D, formulation development, and bioequivalence testing.