Camptothecin Analogs for Cancer Therapy

DESCRIPTION (provided by applicant): 7-butyl-10-aminocamptothecin (BACPT) and its water-soluble dipeptide pro-drug, are novel camptothecins that were designed to be used in the treatment of childhood neuroblastoma. These CPT analogs are lactones that have increased activity in acidic hypoxia tissues, characteristic of fast growing cancers that characteristically out grow their blood supply. Preliminary in vitro and in vivo studies are presented to support documenting other tumor models that might be more sensitive. The specific objectives of this Phase I study will be to: 1. Synthesize 7-butyl-10-aminocamptothecin (BACPT) and its water-soluble dipeptide pro-drug, BACPTDP in 100 g quantities - sufficient for preclinical studies. 2. Verify the anticancer profile in xenograft studies. 3. Develop the analytical assays required to document purity and stability and develop/validate protocols for pharmacokinetic studies. Upon completion of these studies a Phase II application will be submitted for completion of preclinical studies required for IND submission. BACPT and BACPTDP are novel camptothecins that were originally designed at Duke University to be used in the treatment of childhood neuroblastoma. Subsequently, DEKK-TEC has partnered with Duke and Research Triangle Institute (RTI) to complete the pre-clinical development, prepare the IND and ready the products for a Phase 1 clinical trial. Prior to the latter, DEKK-TEC proposes screening the analogs in a wide spectrum of tumor models to insure the best cancer applications for the products.