Experimental Identification of Promiscuous, Aggregate-Forming Screening Hits

Many screening methods have been developed to identify novel inhibitors for drug design. Although both virtual and experimental high throughput approaches have successfully discovered new lead compounds [1-8], it has become clear that screening hit lists are plagued by problematic molecules. Often, these compounds display perplexing behaviors, such as a flat structure-activity relationship [2], time-dependent activity, and steep inhibition curves [9]. Because of these undesirable properties, many screening hits end up as developmental dead ends, often after considerable time and resources have been devoted to them.