Overview:

Identification of metabolic soft spots in early stage ADME screening should accelerate drug discovery via a reduction in synthetic cycles and/or abandonment of problematic templates earlier in the discovery process. Currently high-throughput metabolic stability studies in microsomes are used to guide synthesis when there is need to modulate clearance. Providing structural information alongside clearance data will allow design chemists to make more streamlined synthesis decisions. HRMS technology coupled with software automation tools that leverage real time multiple defect filtering (MMDF) technology have significantly increased the throughput speed of soft spot identification studies. Here we describe two software packages, MetabolitePilot® (AB SCIEX) and MassMetasite® (Molecular Discovery), that were investigated in an effort to develop a high-content metabolic stability screening model.