17 alpha-propionate

Acne vulgaris is a disorder of the pilosebaceous unit in which the androgens contribute to its onset and persistence. Though the use of antiandrogens is potentially effective; topical use of antiandrogens are not available on the market. Cortexolone 17a-propionate (CB-03-01) is a new potent topical antiandrogen potentially useful in acne vulgaris. CB-03-01 is a new chemical entity that acts at the level of the skin androgen receptor, which blocks testosterone and di-hydrotestosterone from binding to the receptor in the cell.
In vitro: The aim of one in vitro study was to investigate the antiandrogenic activity of a new monoester of cortexolone, cortexolone 17alpha-propionate. Although the compound displayed a strong local antiandrogenic activity in hamster's flank organ test. Its pharmacological activity seemed to be primarily related to its ability to antagonistically compete at androgen receptor level; nevertheless its primary pharmacological target needs to be further investigated. The topical activity of cortexolone 17alpha-propionate with the apparent absence of systemic effects makes this compound to have the potential of representing a novel and safe therapeutic approach for androgen-dependent skin disorders. [1].
In vivo: Cortexolone 17alpha-propionate displayed a strong local antiandrogenic activity in hamster's flank organ test, however, it did not exhibit antiandrogenic activity in rats, nor did it affect gonadotropins hypersecretion. As topical antiandrogen, the steroid resulted about 4 times more active than progesterone and, when compared to known antiandrogen standards, it was about 3 times more potent than flutamide, about 2 times more effective than finasteride and approximately as active as cyproterone acetate. Its pharmacological activity seemed to be primarily related to its ability to antagonistically compete at androgen receptor level; nevertheless its primary pharmacological target needs to be further investigated [1].
Clinical trial: In 2011, Trifu et al. evaluated the safety and efficacy of cortexolone 17alpha-propionate 1% cream in acne vulgaris in comparison to placebo and to tretinoin 0.05% cream. A total of 77 male subjects were randomized to receive cortexolone 17alpha-propionate 1% cream, tretinoin 0.05% cream or placebo once nightly for 8 weeks. cortexolone 17alpha-propionate 1% cream was statistically better than placebo in reducing total lesion count, inflammatory lesion count  and Acne Severity Index, without any major side effects. Further, cortexolone 17alpha-propionate 1% cream showed a faster onset of all the abovementioned improvements and was clinically more effective than tretinoin 0.05% cream, although the results were not statistically significant [2]
Reference:
[1] Celasco G, Moro L, Bozzella R, Ferraboschi P, Bartorelli L, Quattrocchi C, Nicoletti F. Biological profile of cortexolone 17alpha-propionate (CB-03-01), a new topical and peripherally selective androgen antagonist. Arzneimittelforschung. 2004;54(12):881-6.
[2] Trifu V, Tiplica GS, Naumescu E, Zalupca L, Moro L, Celasco G. 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;165(1):177-83.