Medicinal Chemistry Core

Division Of Basic Sciences - Nci

Investigators

Abstract

There is a need for medicinal chemistry to support translational cancer research ongoing within CCR. The development of new small molecules to target clinically important targets requires considerable effort in chemistry to improve, optimize, and understand the activity of drug candidates. Currently, within research labs and screening centers in CCR and NCATS there is considerable screening infrastructure available to identify hit compounds with micromolar potency. However, such hits do not have suitable properties (such as potency, cell permeability, or ADME) to be used as selective chemical probes or to be translated to the clinic. Thus, projects often stall as there is no mechanism to advance these molecules beyond the discovery stage. In order to develop a compound, hits are optimized to leads and eventually clinical candidates through medicinal chemistry efforts. A hit-to-lead project might require the chemical synthesis and evaluation of 100-1000 compounds to generate a compound with nanomolar potency. Development of this lead to a clinical candidate with in vivo activity and suitable ADME/Tox properties then requires a second round of optimization, again requiring the synthesis of 100-1000 more compounds and the accompanying assays. One or both of these steps is required to de-risk a compound, making it attractive for potential licensing or internal clinical development. This type of drug discovery work is beyond the resources, expertise, and scientific scope of individual CCR investigators.