Hanno Wild

Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits

Drug-like and lead-like hits derived from HTS campaigns provide good starting points for lead optimization. However, too strong emphasis on potency as hit-selection parameter might hamper the success of such projects. A detailed absorption, distribution, metabolism, excretion and toxicology (ADME-Tox) profiling is needed to help identify hits with a minimum number of (known) liabilities. This is particularly true for drug-like hits. Herein, we describe how to break down large numbers of screening hits and we provide a comprehensive overview of the strengths and weaknesses for each structural class. The overall profile (e.g. ligand efficiency, selectivity and ADME-Tox) is the distinctive feature that will define the priority for follow-up.

“Collaborative Innovation”—Regaining the Edge in Drug Discovery

It is well documented that the pharmaceutical industry currently faces serious challenges as indicated by decreasing output and rising costs of new medical entities. This development is based on the fact that targets and diseases that are now being pursued to address unmet medical needs are more complex than those in the past. Heightened risk perception in society, increasing regulatory requirements, and reimbursement issues associated with increasing overall healthcare costs have exacerbated this situation, and the demonstration of the net clinical benefit of new drugs increasingly requires large and expensive late-phase clinical studies. While these issues are relatively easy to describe, it is much more challenging to provide solutions that will help to pave the way towards breakthrough innovation and cost control. Some notable recommendations include the reduction of nontechnical attrition (project terminations for business or strategic reasons), the combination of the best features of small and large pharma companies, and the promotion of internal innovation by favoring leadership (inspiration) over management (controlling). 7] The special role of chemistry for the future of the pharmaceutical industry has also been discussed. Herein we would like to focus on “Collaborative Innovation”, a concept we expect to provide significant contributions to help address these challenges. This approach should enable the generation of breakthrough innovations based on scientific issues too complex for one organization alone to handle in a cost-efficient manner. Evolution in the Making—From the Extended Workbench to Strategic Alliances