Synthesis and MAPK Kinase Inhibitiory Activities in Prostate Tumors

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

Prostate cancer is the most commonly diagnosed cancer in American men. In 2005, an estimated[unreadable] 230,900 new cases will be diagnosed. Although androgen ablation is highly effective palliative therapy, all men[unreadable] eventually relapse due to the presence of androgen independent prostate cancer cells within metastatic sites.[unreadable] Currently there is no therapy that effectively eliminates these androgen independent prostate cancer cells.[unreadable] Identification of the signal transduction pathways responsible for survival and proliferation of androgen[unreadable] independent prostate cancer cells is critical for rational drug development. In preliminary studies, imido-substituted[unreadable] 2-chloro-1,4-naphthoquinones have been identified, that are selective inhibitors of Mek-1. Over the[unreadable] past year approximately 75 napthoquinone analogs have been synthesized and tested for cytotoxicity against a panel of[unreadable] human prostate cancer cell lines. These studies have identified certain structure-cytotoxicity relationships that[unreadable] will be exploited in synthesis of additional analogs. The goal of the studies is to identify potent cytotoxic imido-substituted[unreadable] napthoquinones that will be analyzed for inhibitory activity against MEK-1 and other membrane[unreadable] bound and intracellular protein kinases.