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ANTI-ANDROGENIC MECHANISM OF A NEW COMPOUND

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41CA097647-01
Agency Tracking Number: CA097647
Amount: $99,750.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 2002
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
ANDROSCIENCE CORPORATION 11175 FLINTKOTE AVE, STE F
SAN DIEGO, CA 92121
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 CHARLES SHIH
 (858) 638-7230
 CYSHIH@ANDROSCIENCE.COM
Business Contact
 CHARLES SHIH
Phone: (858) 638-7230
Email: CYSHIH@ANDROSCIENCE.COM
Research Institution
 George Whipple Laboratory for Cancer Research
 
George Whipple Laboratory for Cancer Research
Rochester, NY 14642
United States

 Domestic Nonprofit Research Organization
Abstract

DESCRIPTION (provided by applicant): Androgen blockage therapy may relieve the symptom of an advanced, localized prostate tumor; however, once the tumor evolves into a hormone-refractory stage, there is no effective treatment. A continuous activation of AR by antiandrogens (used in androgen blockage therapy) or other "nonconventional" agonists may contribute to prostate cancer progression in patients after androgen deprivation. Conceptually, pharmacological agents blocking AR function evoked by not only testicular androgens but also other agonists would have a superior capacity to decrease prostate cancer incidence at both the androgen-sensitive and -insensitive stages. We recently found that a derivative of diferuloylmethane (Compound 4) inhibited dihydrotestosterone-induced androgen receptor transactivation in human prostate cancer cells. This agent also suppressed dihydrotestosterone-induced LNCaP cell growth. Furthermore, Compound 4 was effective in decreasing LNCaP cell growth and AR transactivation stimulated by hydroxyflutamide, a widely used antiandrogen. Based upon these preliminary data, we propose in this study to:

(1) Further test whether Compound 4 abolishes AR function elicited by cyproterone acetate, estradiol, dehydroepiandrosterone, and androstenediol. These antiandrogen or steroid hormones have been documented to have residual AR agonist activity and may exist in significant amounts in patients after androgen blockage therapy.

(2) Explore the mechanisms of action of Compound 4 to antagonize the AR. Compound 4 may disrupt the AR pathway at multiple steps. In this preliminary study, we will examine the most likely mechanisms- whether Compound 4 blocks androgen-induced biological response via a down-regulation of AR expression, or via a competitive suppression of testicular androgens' binding to the receptor.

The discovery of a novel antiandrogen capable of preventing both androgen-dependent and androgen-independent prostate cancer may have a direct impact in clinical application.

* Information listed above is at the time of submission. *

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