Delving into the Latest Updates on Turosteride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

FCE 26073, FCE-26073

Target

5α-reductase

Action

inhibitors

Mechanism

5α-reductase inhibitors(Steroid 5 alpha reductase inhibitors)

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication-

Inactive Indication

Prostatic CancerProstatic Hyperplasia

Originator Organization

Pfizer Inc.

Active Organization-

Inactive Organization

Pfizer Inc.

Pharmacia Corp.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC27H45N3O3

InChIKeyWMPQMBUXZHMEFZ-YJPJVVPASA-N

CAS Registry137099-09-3

Inhibition of 5alpha-reductase type 1 has been considered to be a promising target for treatment of androgen-dependent skin disorders, however, currently published clinical results on acne treatment are rather disappointing. In this study, the influence of selective inhibitors of 5alpha-reductase on testosterone metabolism within SZ95 sebocytes and HaCaT keratinocytes IN VITRO was investigated. In both cell types, the isotype 1 inhibitor MK386 completely inhibited the conversion of testosterone to 5alpha-dihydrotestosterone in concentrations higher than 10 (-9) M. Inhibitors of the isotype 2 such as finasteride, dihydrofinasteride, and turosteride, were >100-fold less active, while, as expected, androgen receptor inhibitors did not affect the 5alpha-reductase activity. MK386, but not finasteride, reduced testosterone-stimulated proliferation and slightly reduced the testosterone-induced increase in the amount of SZ95 sebocyte proteins. The androgen receptor inhibitor cyproterone acetate exhibited no effect on testosterone-induced proliferation, but inhibited the 5alpha-dihydrotestosterone-induced sebocyte proliferation. Our experimental findings and the existing clinical results indicate that the inhibition of 5alpha-reductase activity alone may be insufficient to reduce overall sebocyte activity and improve acne lesions.

01 Jun 1998·The ProstateQ3 · MEDICINE

Effect of early treatment of prostate cancer with the 5α-reductase inhibitor turosteride in Dunning R3327 prostatic carcinoma in rats

Q3 · MEDICINE

Article

Author: Donata Giudici ; Enrico di Salle ; Tiziana Zaccheo

BACKGROUND:

Turosteride, a selective 5alpha-reductase inhibitor, was reported to be effective in inhibiting the growth of established tumors in the Dunning R3327 rat prostatic carcinoma model. We evaluated the preventive effect of turosteride when administered during the latency period in this prostatic tumor model.

METHODS:

Turosteride was given orally, 6 days a week for 10-15 weeks, starting at different times: 1) 5 weeks after tumor implantation, when tumors were not yet palpable, or 2) 1 day after tumor implantation. In each experiment, one group of animals was castrated on the first treatment day.

RESULTS:

When treatment started 5 weeks after tumor implantation, neither turosteride (at 50 and 200 mg/kg/day) nor castration reduced tumor incidence (91-100%). Tumor growth was reduced in groups treated with the highest dose of turosteride and in castrated rats. When treatment started 1 day after tumor implantation, castration resulted in a 62% tumor incidence compared to 100% in controls, while turosteride at 200 mg/kg/day was not effective in reducing tumor incidence. However, as in the previous experiment, the compound was highly effective in reducing tumor growth.

CONCLUSIONS:

The antitumor activity profile of turosteride seems not to be related to the timing of treatment. Given either 5 weeks or 1 day after tumor implantation, the compound did not reduce tumor take, while it maintained effective tumor growth-inhibiting activity in both cases.

01 Feb 1997·The ProstateQ3 · MEDICINE

Effect of turosteride, a 5α-reductase inhibitor, on the Dunning R3327 rat prostatic carcinoma

Q3 · MEDICINE

Article

Author: D. Giudici ; E. di Salle ; T. Zaccheo

BACKGROUND:

Turosteride (FCE 26073) is a new, potent, and selective 5 alpha-reductase inhibitor. We have investigated its effect on tumor growth, organ weight, and serum hormone levels in rats bearing the androgen sensitive Dunning R3327 prostatic carcinoma.

METHODS:

Animals with tumor diameters of 0.5-1.5 cm were treated for 9 weeks with turosteride (50 and 200 mg/kg/day, 6 days a week, orally), flutamide (25 mg/kg/day, 6 days a week, orally), and leuprolide (300 micrograms/rat, every 3 weeks, subcutaneously) or they were castrated.

RESULTS:

Turosteride was ineffective at the dose of 50 mg/kg/day, whereas at 200 mg/kg/ day it significantly decreased tumor growth by 45%. Flutamide and leuprolide were highly effective in reducing tumor growth (70 and 77%), although their effect was slightly lower than that of castration (85%). A significant reduction of ventral prostate weight occurred in rats treated with turosteride at 50 and 200 mg/kg/day (53% and 60%). In contrast to leuprolide and castration, the inhibitory effect of turosteride on tumor growth and prostate weight was not associated to any decrease in serum testosterone.

CONCLUSIONS:

Turosteride has antitumor activity on Dunning prostatic tumor growth and its role in prostatic cancer treatment is worthy of further investigation.

100 Deals associated with Turosteride

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	Turosteride	-	-

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Phase 2	Italy	Pharmacia Corp.	-
Prostatic Cancer	Phase 2	-	Pfizer Inc.	-
Prostatic Hyperplasia	Phase 2	Italy	Pharmacia Corp.	-
Prostatic Hyperplasia	Phase 2	-	Pfizer Inc.	-