We have continued our investigation on the effects of MSD L651582 and recently have developed chemical modifications of L651582. In addition, we have initiated preclinical development of L651582 with the projection of submitting an IND application and Phase I clinical trial protocol to the FDA within this annual report year. We have shown previously that L651582 inhibits proliferation of a variety of cancer cell lines and prevents several steps in the process of tumor cell invasion and metastasis including adhesion and migration. We demonstrated the anti-proliferative and anti-metastatic effects of L651582 in animal models of spontaneous and experimental metastasis and tumorigenesis. We have expanded our in vitro observations to include several new cancer cell lines, effects on laminin-stimulated adhesion and migration, direct effects of phospholipases A2 and C and calcium modulation in noncancer models, and have developed analogs of the parent compound. Animal studies are in progress to evaluate the clinical efficacy of the analogs. A continuation-in-part has been submitted for the use patent application and a new patent application has been made describing the analog work. In in vivo studies, we have shown that L651582 inhibits experimental pulmonary metastases due to HT-29 human colon carcinoma.
