The SDF™ platform is the technology for making drug candidates from lead compounds. The platform applies X-ray crystallography to get complex structural information of a target protein and lead compounds, informatics to design new compounds with better activities and physiological properties, and medicinal chemistry to synthesize them. To choose preclinical candidates, selected lead compounds are further evaluated through in vitro and in vivo pharmacokinetics, pharmacodynamics, and toxicological studies. We experimentally determined binding modes of the lead compounds to the target proteins by X-ray crystallography. The structures of target proteins bound with lead compounds clearly show the binding modes of the leads and key interactions between the leads and proteins at the atomic level.

To avoid potential side effects from drug candidates, the selectivity is optimally designed through in-house technology. Side effects of drug molecules can be caused by various reasons. A major reason among them is referred as off-target effects which is the binding of drug molecules to the other proteins rather than the target protein, resulting in unwanted effects. Since the master scaffolds theoretically bind to all the proteins in the family, this issue has been studied throughly using structural information and more precisely, structural differences of the proteins in the family. Although the proteins in a specific family have very similar active sites, in many cases, there are unique differences to generate selectivity. We can exploit such differences to optimize drug molecules to boost their selectivity which in turn, will decrease unnecessary side effects.

Then, we carry out the design and synthesis of the compounds on the basis of binding modes. Derivatives of the lead compounds containing functional groups that can improve bioactivity, selectivity, and physicochemical properties are designed and synthesized. The resulting compounds are further evaluated using target enzyme assays, cell-based assays, DMPK, early toxicity, and pharmacological evaluations.