RU-58841

RU-58841 (also known as PSK-3841 or HMR-3841) is a nonsteroidal anti-androgen compound originally developed by Roussel Uclaf in the 1980s for topical treatment of androgen-dependent conditions. The compound functions as a competitive androgen receptor antagonist with high affinity for androgen receptors in hair follicles and sebaceous glands. RU-58841 demonstrates a relative binding affinity of 5% compared to DHT and exhibits a notably short in vivo half-life of less than one hour, making it unsuitable for systemic use but ideal for topical application. The mechanism involves blocking dihydrotestosterone (DHT) from binding to androgen receptors in dermal papilla cells, thereby preventing follicular miniaturization characteristic of androgenetic alopecia. Preclinical studies in animal models demonstrated potent efficacy, with 60% reduction in sebaceous gland size in hamsters and significant hair regrowth in stumptailed macaques without systemic antiandrogenic effects. Human clinical trials conducted by ProStrakan (Phase I with 30 subjects and Phase IIa with 120 subjects) reportedly showed equivalent or better hair growth compared to finasteride after six months of treatment with 2.5% or 5% topical solutions applied once daily. However, these clinical trial results were never formally published in peer-reviewed journals, and development was discontinued following corporate acquisition. RU-58841 is not FDA-approved and no regulatory agency has authorized its use in humans. Despite lack of approval, the compound is available through research chemical suppliers and is used off-label by individuals seeking alternatives to approved treatments like finasteride and minoxidil.

Hair Growth and Follicle Stimulation

• Significant hair regrowth in primate models: Topical application to bald stumptailed macaques produced potent increases in hair density, thickness, and length without detectable systemic effects, demonstrating local antiandrogenic activity ^[2]
• Enhanced follicular activity in human grafts: In controlled studies using balding human scalp grafts on testosterone-conditioned nude mice, 28% of RU58841-treated follicles showed a second growth cycle compared to only 7% in controls, with significantly higher linear hair growth rates (P<0.04) ^[1]
• Superior or equivalent efficacy to finasteride: Phase IIa clinical trials with 120 participants demonstrated that six months of topical treatment (2.5% or 5% solutions applied once daily) achieved equivalent or better net hair growth compared to oral finasteride, though results remain unpublished [Clinical trial data]
• Prevention of DHT-induced miniaturization: As a competitive androgen receptor antagonist with potency comparable to hydroxyflutamide, RU58841 blocks DHT activation of androgen receptors in dermal papilla cells, preventing the progressive follicular miniaturization that characterizes androgenetic alopecia ^[2][9]

Sebaceous Gland Regulation

• Potent dose-dependent sebaceous gland regression: Achieved maximal 60% reduction in sebaceous gland size in Syrian hamster flank organ model at doses as low as 10 micrograms per animal ^[5]
• Localized action without systemic effects: Sebaceous gland inhibition occurred without effects on contralateral untreated sites or androgen-sensitive organs like the prostate, demonstrating true topical selectivity ^[5][4]
• Reversible suppression: Inhibited sebaceous glands returned to normal size within 4 weeks after treatment cessation, indicating controlled and reversible mechanism of action ^[5]
• Superior efficacy among antiandrogens: Ranked most effective among tested compounds (RU 58841 > RU 56187 > RU 38882 > cyproterone acetate) in comparative studies of androgen receptor inhibitors ^[5]
• Effective counteraction of endogenous androgens: Successfully suppressed sebaceous gland growth in male fuzzy rats, inducing glandular and ductal regression equivalent to castration levels without affecting prostate tissue ^[4]

Mechanism of Action Benefits

• Competitive androgen receptor inhibition: Displays competitively suppressive effects on DHT-induced androgen receptor activation with potency comparable to hydroxyflutamide in human prostate PC3 cells ^[2]
• High receptor affinity: Demonstrates high binding affinity for hamster prostate and flank organ androgen receptors, ensuring effective blockade of androgen signaling ^[3]
• Prevention of paracrine signaling cascade: Blocks androgen receptor-mediated production of inhibitory paracrine factors (TGF-β1, TGF-β2, DKK-1) in dermal papilla cells that suppress hair follicle growth and promote miniaturization ^[9]
• Short half-life advantages: In vivo half-life of less than one hour prevents extensive hepatic metabolism and systemic distribution, enabling effective regional treatment without systemic antiandrogenic activity ^[3]

Safety and Tolerability Profile

• Minimal systemic absorption: Designed for topical use with pharmacokinetic properties that limit systemic exposure and prevent formation of active metabolites through N-dealkylation pathway ^[3]
• No systemic antiandrogenic effects: Clinical trials reported no systemic anti-androgenic effects despite local efficacy, avoiding side effects associated with systemic antiandrogen therapy [Clinical trial data]
• Well-tolerated in human trials: Phase I (30 subjects, 4 weeks) and Phase IIa (120 subjects, 6 months) studies reportedly showed good tolerance, though detailed safety data remains unpublished [Clinical trial data]
• Localized site-specific activity: Animal studies consistently demonstrated treatment effects limited to application sites without affecting distant androgen-sensitive tissues ^[4][5]

Regulatory Status and Approval

• Not FDA-approved: RU-58841 has not been approved by the FDA or any other regulatory agency for therapeutic use in humans [General knowledge]
• Discontinued development: Clinical development was halted following ProStrakan's acquisition by Kyowa Kirin, with the Phase III trial never initiated despite promising Phase IIa results [Clinical trial history]
• Unpublished clinical data: Results from human Phase I and Phase IIa clinical trials were never formally published in peer-reviewed scientific journals, creating significant gaps in safety and efficacy documentation [Literature review]
• Research chemical status: Currently available only through research chemical suppliers and compounding sources, marketed for research purposes rather than human therapeutic use [General knowledge]

Clinical Safety Evidence

• No systemic antiandrogenic effects reported: Phase I (30 subjects over 4 weeks with 5% solution twice daily) and Phase IIa (120 subjects over 6 months with 2.5% or 5% solutions once daily) trials reportedly showed no systemic anti-androgenic effects, though detailed safety data remains unavailable [Clinical trial summaries]
• Well-tolerated in trials: Available information indicates treatments were well-tolerated, but absence of published data prevents comprehensive safety assessment [Clinical trial summaries]
• Limited long-term safety data: Maximum study duration of 6 months in Phase IIa provides insufficient information about long-term safety with extended use [Clinical trial summaries]

Pharmacokinetic Safety Features

• Short half-life (<1 hour): Rapid metabolism limits systemic exposure and accumulation, reducing potential for systemic side effects ^[3]
• Topical-only suitability: Brief half-life makes compound unsuitable for oral systemic administration, inherently limiting exposure to application sites ^[3]
• Metabolic profile: Topical application avoids formation of active N-dealkylated metabolites that would possess antiandrogenic properties if systemically administered ^[3]
• Localized activity: Pharmacokinetic properties enable effective regional treatment without systemic androgen receptor blockade ^[3]

Preclinical Safety Observations

• No effects on androgen-sensitive organs: Studies in hamsters and rats demonstrated no effects on prostate or other systemic androgen-dependent tissues despite local efficacy ^[4][5]
• Reversible effects: Sebaceous gland inhibition fully reversed within 4 weeks of treatment cessation, indicating no permanent tissue alterations ^[5]
• No contralateral effects: Unilateral application in animal models produced no effects on untreated contralateral sites, confirming minimal systemic distribution ^[5]

Safety Concerns and Unknowns

• Lack of comprehensive toxicology data: Absence of published preclinical toxicology studies limits understanding of potential risks
• Unknown impurity profiles: Non-pharmaceutical grade products from research chemical suppliers may contain unknown impurities or inconsistent purity
• No quality control standards: Lack of regulatory oversight means no standardized manufacturing, testing, or quality control requirements
• Unknown long-term effects: No published data on safety beyond 6 months of continuous use
• Potential for systemic absorption: While designed for topical use, actual systemic absorption in humans has not been comprehensively characterized in published literature
• Cardiac safety unknown: No published electrocardiographic or cardiovascular monitoring data from human trials
• Reproductive effects unclear: Potential effects on male fertility, testosterone levels, and reproductive function in long-term users remain uncharacterized
• Drug interaction data lacking: No published studies examining interactions with other medications or topical treatments

Theoretical Risks

• Androgen receptor blockade effects: While topical application limits systemic exposure, any absorbed compound could theoretically produce antiandrogenic effects including decreased libido, erectile dysfunction, or gynecomastia
• Skin reactions: Potential for contact dermatitis, irritation, or sensitization reactions at application sites, though incidence rates are not documented
• Hormonal feedback effects: Unknown whether local androgen receptor blockade could trigger compensatory hormonal responses

Special Populations

• Women: Safety in women, particularly those of childbearing potential, has not been adequately studied
• Pediatric use: No safety data in individuals under 18 years of age
• Elderly: Safety profile in older adults not specifically characterized
• Medical conditions: Safety in individuals with liver disease, kidney disease, cardiovascular conditions, or hormonal disorders is unknown