Clascoterone is a novel, very effective topical antiandrogen that might help treat acne vulgaris. Very well tolerated, clascoterone 1% cream outperformed placebo clinically in TLC (P = 0·0017), ILC (P = 0·0134), and ASI (P = 0·0090). more efficient than the control medication. Additionally, the solution improves all of the previously listed metrics by 50% faster.

Absorption, Distribution and Excretion
Upon topical application, clascoteronet permeates the skin to the dermal levels with minimal systemic absorption. In clinical trials, adult subjects with moderate to severe facial acne vulgaris received twice-daily topical application of six grams of clascoterone. The steady-state concentrations of the drug were reached within five days. Following two weeks, the mean ± SD Cmax was 4.5 ± 2.9 ng/mL and the mean ± SD area under the plasma concentration-time over the dosing interval (AUCꞇ) was 37.1 ± 22.3 h*ng/mL. The mean ± SD average plasma concentration (Cavg) was 3.1 ± 1.9 ng/mL.
Excretion of clascoterone has not been fully characterized in humans. Upon topical application, clascoterone is quickly hydrolyzed in the epidermis.
There is no information available on the volume of distribution.
There is limited information on clearance of clascoterone.

---

Metabolism / Metabolites
According to _in vitro_ and clinical studies, the main possible primary metabolite of clascoterone is cortexolone, which is an inactive metabolite. The plasma concentrations of cortexolone were generally below or near the lower limit of quantitation (0.5 ng/mL). Although clascoterone penetrates the skin, the systemic activity of the drug is limited due to rapid hydrolysis of clascoterone into the inactive metabolite by skin and plasma esterases, namely carboxylesterase.

---

Biological Half-Life
There is limited information on the half life of clascoterone.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of clascoterone during breastfeeding. However, because it is poorly absorbed from the skin and 84% to 89% protein bound, amounts in breastmilk are probably low and would not be expected to cause any adverse effects in breastfed infants. Avoid application to the nipple area and ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Protein Binding
Clascoterone is 84% to 89% bound to plasma proteins _in vitro_, regardless of drug concentrations.

[1]. Cortexolone 17伪-propionate 1% cream, a new potent antiandrogen for topical treatment of acne vulgaris. A pilot randomized, double-blind comparative study vs. placebo and tretinoin 0路05% cream. Br J Dermatol. 2011 Jul;165(1):177-83.

[2]. Cortexolone 17α-propionate 1% cream, a new potent antiandrogen for topical treatment of acne vulgaris. A pilot randomized, double-blind comparative study vs. placebo and tretinoin 0·05% cream. Br J Dermatol. 2011 Jul;165(1):177-83.

[3]. Biological profile of cortexolone 17alpha-propionate (CB-03-01), a new topical and peripherally selective androgen antagonist. Arzneimittelforschung. 2004;54(12):881-6.

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.
Clascoterone is an Androgen Receptor Inhibitor. The mechanism of action of clascoterone is as an Androgen Receptor Antagonist.

---

Drug Indication
Clascoterone is indicated for the topical treatment of acne vulgaris in patients 12 years of age and older.

---

Mechanism of Action
Acne is a multifactorial skin condition characterized by excess sebum production, epithelial hyperkeratinization, proliferation of the skin commensal bacteria, and inflammation. Circulating and locally synthesized natural ligands, testosterone and dihydrotestosterone (DHT), serve as causative factors in both males and females. Upon binding of DHT, the DHT-androgen receptor complex dimerizes and translocates to the nucleus where it promotes the transcription of genes involved in acne pathogenesis, including proliferation and differentiation of sebocytes, excess sebum production, and inflammatory cytokine production. Clascoterone is a potent antagonist at ARs and competes for androgens in binding to the receptor, thereby inhibiting downstream signalling of ARs that promote acne. Androgenetic alopecia is also an androgen-dependent and highly genetic condition. Dihydrotestosterone (DHT) binds to ARs expressed on dermal papilla cells (DPC) in the scalp to induce AR-mediated transcription of genes that contribute to androgenic alopecia. By blocking the interaction between DHT and aARs, clascoterone inhibits AR-regulated transcription and DHT-induced IL-6 synthesis.

---

Pharmacodynamics
Clascoterone exerts anti-androgenic effects by working as an antagonist at androgen receptors (ARs) expressed throughout the skin, including sebaceous glands, sebocytes, and dermal papilla cells. Clascoterone blocks the effects of testosterone and dihydrotestosterone (DHT), which are androgens that bind to the ARs and contribute to the development of androgen-dependent conditions such as acne and alopecia. _In vitro_, the antiandrogenic effects of clascoterone in human primary sebocytes occurred in a dose-dependent manner. Clascoterone mediates selective topical activity by mainly targeting androgen receptors at the site of application. It has limited systemic effects. In clinical trials, HPA axis suppression was observed as a 30-minute post-stimulation serum cortisol level of ≤18 mcg/dL in 5% of adult subjects and 9% of adolescent subjects with acne vulgaris following two weeks of topical treatment of clascoterone. HPA axis function returned to normal following the discontinuation of drug treatment.

C24H34O5

402.53

402.24

C, 71.61; H, 8.51; O, 19.87

19608-29-8

19608-29-8;152-58-9;

11750009

White to light yellow solid powder

1.2±0.1 g/cm3

538.9±50.0 °C at 760 mmHg

179.3±23.6 °C

0.0±3.3 mmHg at 25°C

1.555

3.76

1

5

5

29

769

6

O=C1CC[C@@]2(C)C(CC[C@]3([H])[C@]2([H])CC[C@@]4(C)[C@@]3([H])CC[C@@]4(C(CO)=O)OC(CC)=O)=C1

GPNHMOZDMYNCPO-PDUMRIMRSA-N

InChI=1S/C24H34O5/c1-4-21(28)29-24(20(27)14-25)12-9-19-17-6-5-15-13-16(26)7-10-22(15,2)18(17)8-11-23(19,24)3/h13,17-19,25H,4-12,14H2,1-3H3/t17-,18+,19+,22+,23+,24+/m1/s1

[(8R,9S,10R,13S,14S,17R)-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] propanoate

CB03-01 CB 03-01 CB-03-01

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~248.43 mM)

Solubility in Formulation 1: ≥ 2.75 mg/mL (6.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.75 mg/mL (6.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.75 mg/mL (6.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)