Description

RU58841 Liquid

 

 

CAS Number	154992-24-2
Other Names	RU 58841, RU-58841, 0D8FJQ0ADW, CHEMBL9337, PSK-3841; HMR-3841, UNII-0D8FJQ0ADW
IUPAC Name	4-[3-(4-hydroxybutyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
Molecular Formula	C₁₇H₁₈F₃N₃O₃
Molecular Weight	369.34
Purity	≥99% Pure (LC-MS)
Application	Topical
Liquid Availability	30mL 5% KB solution 30mL 5% plant-based solution 30mL 8% KB solution 30mL 8% plant-based solution 60mL 5% KB solution 60mL 5% plant-based solution  60mL 8% KB solution  60mL 8% plant-based solution
Powder Availability	5 grams  10 grams
Gel Availability	N/A
Storage	Store in cool dry environment, away from direct sunlight.
Terms	All products are for laboratory developmental research USE ONLY. Products are not for human consumption.

 

RU58841: A topical, localized hair restorative treatment that can outperform finasteride

In the early 1990’s, researchers first synthesized RU-58841 as a novel anti-androgen which can suppress Androgen Receptor signaling [1], [2]. Early research was devoted to potential applications in the treatment of acne, but it soon became clear that its use for pathological hair thinning (ie. androgenic alopecia). Apparently owing to the success of finasteride, RU58841 was abandoned despite the positive and compelling research results showing its success in promoting hair restoration in numerous models of hair loss.

Preclinical Benefits Observed:
1. Targeted, localized therapy on the scalp with minimal systemic effects
2. Suppression of DHT for restoration of hair growth (ie. density, thickness, length)

Selected Preclinical Research:
1. “Evaluation of RU58841 as an anti-androgen in prostate cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques” [3]
The effect of androgen receptor transcriptional activation by RU58841, a nonsteroidal anti-androgen, was studied in the human prostate cancer cell line by and an androgen-responsive reporter construct. The anti-androgens hydroxyflutamide and Casodex, and the antiestrogen, genistein, were studied in parallel for comparison with RU58841. The Androgen Receptor was activated only by the androgen dihydrotestosterone (DHT). Neither the anti-androgens nor antiestrogen can enhance Androgen Receptor activity. Hydroxyflutamide, RU58841, and Casodex, but not genistein, displayed competitively suppressive effects on DHT activation of the Androgen Receptor. The potency of RU58841 was comparable to that of hydroxyflutamide. From this result, topical application of RU58841, which is considered to be a potential therapy for skin diseases, may induce systemic side effects. However, RU58841, on topical application, revealed a potent increase in density, thickening, and length of hair, whereas no systemic effects were detected. Together these results suggest that RU58841 may have potent antagonism to the Androgen Receptor and could be considered as a topically applied active anti-androgen for the treatment of androgen-dependent skin disorders, such as acne, and androgenetic alopecia.

Fig. 1. Folliculogram showing sequential patterns of the relative number of hairs at pretreatment (A) compared to 5 months after RU58841 treatment (B). At pretreatment, most hairs are in telogen phase (T) which is a resting state. However, after 5 months of RU58841 treatment, most hairs are in anagen phase (A5) which is a growth phase. Adapted from Pan et al., Endocrine 9(1):39-43.

This research demonstrated the effectiveness of RU58841 in promoting the hair density, hair thickening, and hair length in a primate model of alopecia relevant to humans. The authors note that RU58841 exerts a dose-dependent effect on follicular regrowth, and this observation indicates that RU58841 should be studied in the clinical setting for androgenic alopecia. The fact that topical application is effective stands in contrast to other antiandrogen such as cyproterone acetate which is inactive in human skin when applied topically. In addition to in vivo topical effects, RU58841 also antagonized testosterone-driven hair loss in vitro.

Fig. 2. Photographs showing effects of topical RU58841 on hair regrowth on bald frontal scalps. Increased density and length of hairs were observed in a scalp at 4 months after treatment with 5% RU 58841 (b) compared with the scalp at the pretreatment time (a). A slight increased density of hairs was noticed in a scalp at 4 months after treatment with 0.5% RU 58841 (d) compared with the scalp at the pretreatment time (c). A control-treated scalp showed no signs of hair regrowth (e) at pretreatment time compared to 4 months later (f). Adapted from Obana et al., Endocrinology 138(1) 356-361.

 

2. “A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice” [4]
Human hair growth can be monitored for several months after the transplantation of scalp samples from men with androgen-dependent alopecia onto hairless mice. Hair production from balding sites has been shown to be inhibited in testosterone-conditioned hairless mice. This research group recently reported a model to study the effect of a new non-steroidal antiandrogen RU58841 on human hair growth. Twenty productive scalp grafts from balding men were maintained for 8 months after grafting on to hairless mice, and hair production was monitored monthly for 6 months. All mice were conditioned by the topical application of testosterone (testosterone propionate, 5 days/week) on their non-grafted flanks. The scalp samples were divided equally according to the estimated hair production potential, which was based on the amount of hair present on the scalp samples before grafting. Each of the two equal groups of grafts was further allocated at random to be treated topically (5 days/week) with either RU58841 1% in ethanol, or ethanol as a control. Twenty-eight active follicles appeared on the 10 control grafts. Among them only two follicles (7%) initiated a second hair cycle. However, the 10 RU58841-treated grafts bore a total of 29 active follicles, and eight of them (28%) showed a second cycle. The values for the linear hair growth rates were significantly higher in the RU58841 treated group. Increased hair growth rates indicate a positive action for topically applied RU58841 on human hair growth from balding men grafted on to hairless mice, and these results encourage a clinical trial to evaluate its potential in the treatment of androgen-dependent alopecia in adult men.

Fig. 1. The time course of linear hair growth rate (LHGR) of hairs collected at monthly intervals after initiation of continuous hair growth. Adapted from Brouwer et al., British Journal of Dermatology 1997; 137: 699-702.

Fig. 2. The time course for the diameter of hairs collected at monthly intervals after the initiation of continuous hair growth. Adapted from Brouwer et al., British Journal of Dermatology 1997; 137: 699-702.

This study notes that while androgen-dependent skin diseases are not life-threatening, they frequently cause distress in adult men. The prescription of antiandrogens by dermatologists is uncommon because such compounds affect many other target tissues. Hence, the ideal antiandrogen should block the effect of innate androgens at the receptor level only, only at the site of application, and in the absence of any systemic effects. Moreover, it should lack any other hormonal or antihormonal activity.
Fortunately, RU58841 is an ideal candidate since it displays an absence of systemic effects in animals at doses up to 100X the local active dose. RU58841 is remarkable due to its specific binding constant to AR, similar to that of testosterone, and 20% higher than cyproterone acetate. Its activity is strictly limited to the site of application: no effects were observed in the contralateral flank, on prostate weight, or on serum testosterone level. This clear-cut distinction between the skin surface activity versus systemic effects.

Umbrella Labs offers RU58841 dissolved in an all-natural solution comprised of low molecular weight plant oil + non-denatured ethanol, which makes it the only all-natural carrier optimized for RU58841 that can be stored at room temperature or (ideally) refrigerated for improved long-term stability.

This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

References
[1] T. Battmann et al., “RU 58841, a new specific topical antiandrogen: A candidate of choice for the treatment of acne, androgenetic alopecia and hirsutism,” J. Steroid Biochem. Mol. Biol., 1994.
[2] G. Teutsch et al., “Non-steroidal antiandrogens: Synthesis and biological profile of high-affinity ligands for the androgen receptor,” J. Steroid Biochem. Mol. Biol., 1994.
[3] H. J. Pan et al., “Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques,” Endocrine, 1998.
[4] B. De Brouwer, C. Tételin, T. Leroy, A. Bonfils, and D. Van Neste, “A controlled study of the effects of RU58841, a non-steroidal antiandrogen, on human hair production by balding scalp grafts maintained on testosterone-conditioned nude mice,” Br. J. Dermatol., 1997.

RU58841 is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.

 

 

 

 

 

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03-16-2023-Umbrella-Labs-RU58841-Certificate-Of-Analysis-COA.pdf

 

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Additional information

Weight	4 oz
Dimensions	3 × 3 × 5 in
Carrier Solution	K&B Solution, Plant Based Solution
Strength	5% Solution, 8% Solution
Size	30 Millilitres (1oz), 60 Millilitres (2oz)