PCK3145 is a synthetic 15-mer peptide derived from Prostate Secretory Protein (PSP94), a protein found in human seminal fluid, which has been shown to inhibit extracellular matrix (ECM) degradation by MMP-9, a matrix metalloproteinase involved in prostate cancer progression. PSP94 is one of three predominant proteins found in human seminal fluid along with PSA and prostate acid phosphatase. Prostate cancer cells express receptors on their surface that selectively binds to PSP94. Exogenous PSP94 inhibits tumor cell growth through an unknown mechanism. Its mode of action may involve activation of apoptosis via a receptor-mediated signal transduction pathway. PCK3145 subserves several functions and appears to work in animal models as an inhibitor of angiogenesis by rapid onset of binding to the laminin receptor in a �hit-and-run� fashion to downregulate Erk, and to reduce plasma MMP-9 levels, as well as the expression of MMP-9 within tumor. In a phase I dose escalating study, patients (pts) with castrate metastatic prostate cancer who failed hormones and chemotherapy were treated at different dose levels and schedules. Pts treated at all dose-levels had precipitous declines in plasma MMP-9 levels while on the drug; these rose once the drug was discontinued. While safe, pts with disease to bone and/or lymph nodes who progressed despite prior treatment with hormones and chemotherapy have radiographically stable disease and lengthening of PSA doubling times for close to two years. These results were unexpected given the natural history of progression for those patients who have failed prior treatment with hormones and/or chemotherapy.