CAN INSILICO SCREENING SYSTEMS PROVIDE US WITH THE TOOLS TO PREDICT THE DMPK PROPERTIES OF DRUGS IN THE DISCOVERY PROCESS?

Although advancements in combinatorial chemistry and high-throughput screening (HTS) have been very effective at producing “lead compounds” against a particular target, these compounds do not necessarily demonstrate acceptable DMPK properties concerning oral absorption, metabolic stability and CYP inhibition. In vitro DMPK studies introducing higher throughput capabilities are very useful but costly in the lead optimization process, and they might have not resulted in an overall increased efficiency in the drug development process. Recent trends in lead optimization are to use virtual screening to generate a drug candidate's DMPK profile. Here we present our experiences about the application of in silico techniques to predict the intestinal absorption, plasma protein binding and CYP inhibition. Applying in silico DMPK analysis early in the drug development cycle should save time and money in alliance with experimentally based methods including HTS, because this enables the virtual redesign of candidates in lead optimization. The sophisticated HTS systems and the integrated in silico approach are set to become partners, each compensating for the weakness of the other, in bringing new drug candidates to market.