The screening of chemical compound libraries has become an essential component of the drug and bioactive agent discovery process. A key feature of chemical compound libraries is their chemical diversity, which refers to the chemical space encompassed by the library. Nearly all drugs and other xenobiotics are transformed into at least one metabolite, and generally more. Such metabolites frequently have distinct biological activities. The present study was directed toward assessing the potential of <i>in situ</i> library pre-metabolism (Pre-Met) as a means to enhance library chemical diversity in a biologically relevant fashion, and to increase the hit rate and informational value of a library screening effort. This demonstration effort focused on whole cell screening for novel antibacterial agents (MRSA), using the NCI Diversity Set V library metabolized using human liver microsomes. Pre-Met library screening provided a substantial number of unique Pre-Met library hits compared to the Un-Met library screen, demonstrating the potential of this approach.

Enhanced chemical diversity through library <i>in situ</i> pre-metabolism: Using biological chemistry for novel lead discovery

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Enhanced chemical diversity through library in situ pre-metabolism: Using biological chemistry for novel lead discovery