Drug Discovery Engine DDE based on natural products

The “NRW Drug Discovery Engine DDE based on natural products” aims to discover innovative drug candidates with therapeutic potential for cancer or metabolic diseases by medicinal chemistry optimization of hits towards preclinical candidates and validation of these candidates. The basis of this project was a collection of natural products with associated biological activity data compiled in the IMD BIOPROFILING® database. A team of experienced experts (INS, LDC) selected promising target-compound combinations with potential applications in the treatment of cancer and metabolic diseases from the IMD BIOPROFILING database. This database contained more than 12 million data points for structures of chemical compounds with associated activity data. Biological assays for multiple cancer and metabolic targets were established and used to validate initial hits. These assays provided also the basis for further SAR studies and med-chem optimization. Significant efforts were invested in mechanistic studies to further validate or de-validate initial hits. In order to identify the most promising hit-target combinations the consortium employed synthesis of chemical analogs (Taros, LDC), proteomic analysis (ISAS) and functional analysis of cellular hits (MPI-Do, LDC, WTZ).