Ru58841

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posted by jcvaughn26

Evaluation of RU58841 as an anti-androgen in prostate PC3 cells and a topical anti-alopecia agent in the bald scalp of stumptailed macaques.

Pan HJ, Wilding G, Uno H, Inui S, Goldsmith L, Messing E, Chang C.

Department of Pathology, University of Rochester Medical Center, NY 14642, USA.

The effect of androgen receptor transcriptional activation by RU58841, a nonsteroidal anti-androgen, was studied in the human prostate cancer PC3 cell line by cotransfection with wild-type androgen receptor (wt AR) and an androgen-responsive reporter (MMTV-ARE-CAT) construct. Anti-and rogens, hydroxyflutamide, and Casodex, and the antiestrogen, genistein, were studied in parallel for comparison with RU58841. The wt AR was activated only by the androgen dihydrotestosterone (DHT). Neither the anti-androgens nor antiestrogen can enhance AR transcriptional activity at 10(-11)-10(-7)M in PC3 cells. Hydroxyflutamide, RU58841, and Casodex, but not genistein, displayed competitively suppressive effects on DHT activation of wt AR. 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 in the macaque model of androgenetic alopecia, whereas no systemic effects were detected. Together our results suggest that RU58841 may have potent antagonism to the wt AR and could be considered as a topically applied active anti-androgen for the treatment of androgen-dependent skin disorders, such as acne, androgenetic alopecia, and hirsutism.

PMID: 9798729 [PubMed - indexed for MEDLINE]

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.

De Brouwer B, Tetelin C, Leroy T, Bonfils A, Van Neste D.

Skin Study Centre, Tournai, Belgium, France.

Human hair growth can be monitored for several months after the transplantation of scalp samples from men with androgen-dependent alopecia on to female nude mice. Hair production from balding sites has been shown to be inhibited in testosterone-conditioned nude mice. We used this recently reported 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 nude mice, and hair production was monitored monthly for 6 months. All mice were conditioned by the topical application of testosterone (testosterone propionate, 300 micrograms in 10 microL; 5 days/week) on the non-grafted flank. 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 blinded solutions of 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 (LHGR) were significantly (P < 0.04) higher in the RU58841-treated group. Recycling and increased LHGR indicate a positive action for RU58841 on human hair growth from balding samples grafted on to testosterone-conditioned nude mice, and encourage a clinical trial to evaluate its potential in the treatment of androgen-dependent alopecia.

PMID: 9415227 [PubMed - indexed for MEDLINE]

This following information has been gathered at Hairsite2 and Hairsite7, as many of our customers have asked for more information on RU and its effect.
RU58841 vs. minoxidil: the scientific evidence for the new readers here...
From: Bryan
Date: 19 May 2001

Comments
"The Effect of Topical RU58841 (Androgen Receptor Blocker) Combined With Minoxidil on Hair Growth in Macaque Androgenetic Alopecia", K. Imamura, A. Bonfils, A. Diani, and H. Uno. Wisconsin Primate Research Center, Univ. Wisconsin, Madison, WI, USA, Hoechst Marion Roussel, Romainvill, France, and Pharmacia-Upjohn, Kalamazoo, MI, USA.

"Our previous studies demonstrated that the treatment with either RU58841 (RU) or minoxidil (M) alone induced significant hair regrowth in the bald stumptail macaques. However, the rate of hair growth has not significantly progressed after 6 months. This implies that M stimulates follicular cell proliferation but is unable to halt androgenetic follicular regression. On the contrary, RU prevents androgenetic follicular regression but appears to have no direct stimulating effect on follicular cell growth.

"The present study was aimed to evaluate the effect of combined RU 5% (RU-5) with M 2% (M-2) or M 5% (M-5) solution on hair regrowth by both photographic recording and micromorphometrical analysis of follicular growth (folliculogram). The vehicle, mixture of propylene glycol, alcohol, and water, was used for both compounds and was applied to the placebo group. Each group has 3 monkeys. The data of hair growth for RU-5, M-2, and M-5 groups were used the results from our previous studies. The results revealed that the initial hair regrowth was noticed as early as 1 month after treatment in RU-5 + M-5 and 2 months in RU-5 + M-2 group. The similar degree of hair growth noticed at 3 months after treatment with RU-5 and M-5 alone. In M-2 group, the hairiness maintained but showed no noticeable regrowth. At 3 months, regrowth of long terminal hairs appeared in both RU-5 + M-2 and RU-5 + M-5 groups and these hairs maintained for 6 to 12 months. The overall rate of anagen conversion conversion and follicular enlargement were higher in combined groups compared to RU-5 and M-5 alone and revealed no significant difference between RU-5 + M-2 and RU-5 + M-5. The follicular growth was not found in M-2 group. Progressive effect of hair growth by combined treatment of antiandrogen with hypertrichotic agent showed most remarkably in early stage, but within one year the overall effects of hair regrowth revealed no significant difference compared to the rate in RU-5 or M-5 alone. Long-term observation will be necessary to find the synergetic effects on the follicular growth."

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