ABSTRACT
Drug discovery and development is notoriously difficult and expensive. Today, improving the productivity of R&D is unanimously recognized as the major challenge that the drug industry faces to maintain its historical growth rate. A number of recent assessments have described the inefficiencies within the industry and outlined many of the causes (1-4). It is now widely recognized that many of the risks carried late into development could, and should, have been dealt with in the earlier discovery phase. Starting in the mid-1990s, the motto in R&D became “fail fast” to avoid the costly late-stage failures in development by eliminating the losers quickly. The industry put in place high-throughput assays for ADMET (absorption,
distribution, metabolism, excretion, and toxicity) to filter out the compounds with clear ADMET liabilities and developed predictive methodologies to select compounds with the least risk from virtual libraries before actual synthesis. The historic process of maximizing potency and selectivity prior to overcoming ADMET and other development liabilities is now superseded with a more balanced approach in which these criteria are examined much earlier (5,6). The expected outcome is a reduction of the cycle time and overall cost of bringing the drug candidates to the market.
