From Computers to Bedside: Computational Chemistry Contributing to FDA Approval

The drug development process is a time‐consuming and expensive endeavor, primarily due to the high attrition rates, with around 9 out of 10 drug candidates failing approval. Computer‐aided drug design is becoming an essential tool in assisting fast and cost‐efficient lead discovery and optimization because it utilizes the knowledge of the three‐dimensional structure of the biological target in the process (structure‐based drug design) or the activity of known binders to the target of interest (ligand‐based drug design). In recent years, significant advances in structure‐based drug design and molecular modeling have contributed to the discovery of several drugs now in the market such as sunitinib (kinase inhibitor, gastrointestinal cancer, Pfizer, 2006), crizotinib (anaplastic lymphoma kinase (ALK) inhibitor, non‐small cell lung cancer (NSCLC), GSK, 2011). In the past, several articles have illustrated computational procedures that guided the design of potent inhibitors, but it has not been clear how these methodologies actually assisted the discovery of drugs that have reached the market. In the current review, we summarize cases of FDA‐approved drugs, the discovery of which was influenced by computer‐aided drug design techniques. We also present novel advanced methods that have significantly advanced medicinal chemistry projects and are expected to bring more FDA approvals in the near future.