Medicinal chemistry   

• Under the direction of Edward Kesicki and Joshua Odingo, former medicinal chemistry group leaders at ICOS. They were involved with teams that discovered three compounds that entered human trials.
• Medicinal chemistry is the link between HTS and preclinical studies, and represents a critical bottleneck in the drug discovery process.
• IDRI's medicinal chemistry facility was completed in March 2008 and is operational for hit-to-lead and lead optimization/SAR.   
• Research activities involve the design, synthesis, purification and characterization of individual compounds for biological evaluation. The process, usually multi-step, is highly technical and labor-intensive but can sometimes be simplified when parallel or combinatorial methods of synthesis are applicable.
• The hits emerging from screens undergo validation to confirm that the structure listed in the database matches that in the sample well. In addition, an authentic pure sample of the compound must be obtained and tested. This will confirm that the observed inhibitory activity can be tied to the listed structure and not to some impurity in the sample well. 
• After validation, the molecule is explored for key structural elements by preparing and testing a set of closely related compounds in a process referred to as hit-to-lead.
• Once a core structure or structural class is established, it serves as a lead for further optimization. This is known as developing a structure-activity relationship, or SAR.
• During SAR, the lead is structurally refined to improve its drug characteristics with a goal to identify a clinical candidate. The compounds prepared at these stages will undergo bioactivity evaluation as well as tests of drug-like characteristics such as metabolic stability, aqueous solubility, cellular absorption, cytochrome P450 interactions, bioavailability, etc.
• Computer-aided drug design (CADD) can also be used to model and predict interactions between target and designed compounds.