The core technology of Rib-X Pharmaceuticals is solving high resolution crystal structures of the ribosome with bound antibiotics. Information collected from these structures is fed into our Closed-loop drug discovery paradigm (see Figure 1). Our computational chemists use the crystal structure data and our proprietary Analog software to search in silico (via the computer) tens of thousands of potential compounds to identify those that will target the ribosome precisely. Winning compounds are further prioritized by their predictive drug-like qualities. The best of these compounds are synthesized by the medicinal chemistry group and are tested for activity by the biology group. Compounds with promising inhibitory activities are then tested by pre-clinical scientists and are given back to the crystallographers for further structural studies. All data are stored in a proprietary database and used by the computational chemists for even more accurate predictions of active compounds.



Figure 1. The Closed-loop approach. Crystallographic structures of compounds bound to the ribosome are analyzed computationally. New compounds that mimic or improve binding and drug-like characteristics are designed, synthesized and tested. Subsequently, Winning compounds' co-crystal structures with the ribosome are subsequently solved. All the data are used computationally in the next round to further improve the winning compounds.