Translational research in a novel anti cancer agent

DESCRIPTION (provided by applicant): Natural products possess the richest source of molecular diversity in existence. In the case of cancer therapeutics, natural products have yielded a significant number of novel and effective cancer treatment and prevent ive agents. As a commercial venture, BCN Biosciences has a commitment to identifying new chemical structures from plants and fungi, and the development of technology to address the difficulty of screening or mining such compounds from complex mixtures that may possess multiple active constituents. We have discovered a novel pheophorbide derived compound which can inhibit tumor growth in a light-independent manner, exhibits no detectable toxicity in mice, and is orally available. We have named this compound AM-101. In this grant application, we outline our plan to further study AM-101 and will pursue the following specific aims: 1) To test the effect of synthetic AM-101 in breast tumor xenograft models. We will use two mouse xenograft models to assess AM-101' s ability to suppress breast cancer growth and/or metastasis. 2) To determine the mechanism(s) of AM-101's action. We will explore potential mechanisms of AM-101's action, including DNA cleavage, apoptosis, cell cycle disruption, protein kinase and angioge nesis inhibition, and interaction with BRCP (Breast Cancer Resistance Protein). We believe that the work in this Phase 1 proposal will lead to successful pre-clinical testing (Phase 2) and eventually human clinical trials. PUBLIC HEALTH RELEVANCE: The Publ ic heath relevance of this work is that it creates new opportunities and possibilities for treating the deadly disease of cancer worldwide.