Treatment for advanced prostate cancer involves the reduction of the patients' levels of testosterone (androgen). Unfortunately, this form of therapy is not curative, and eventually the disease will return in an androgen-independent form. Once the disease is androgen independent, the survival time is approximately 2 years before the patient will succumb to his disease. There are no effective therapies currently available for these patients. In order to develop new therapies, a target must be known. Our laboratory has recently identified a possible target for drug development. This target is supported by pre-existing knowledge that androgen stimulates the growth of prostate cells by activating androgen receptors located in the cell. The activation of the androgen receptor is also linked to the growth of prostate cancer cells and is the basis for androgen withdrawal therapy for patients with prostate cancer. Work in our laboratory and others has yielded results verifying the existence of alternative mechanisms for activating the androgen receptor in the absence of androgens. We have identified a unique region on the androgen receptor that appears to be responsible for its activation and thereby provides a novel therapeutic target. This data provides the rationale for the studies proposed, which include screening and then testing small molecules that may prevent or delay the progression of prostate cancer to androgen independence. We envision that upon conclusion of these studies, we will have identified important lead compounds that can be used to develop new drugs that will delay or prevent the development of androgen-independent prostate cancer.