Overcoming the Challenges of Multi‐Target‐Directed Ligands for Alzheimer's Disease

The concept of multi‐target‐directed ligands has been quite successful within the drug discovery community, due to its potential to better address the multifactorial nature of complex diseases. However, translating one of these ligands into new drugs has turned out generally complicated, even more for the Alzheimer's disease field. Here we describe some of the faced challenges, with specific focus on a number of “culprits” including target selection, pharmacokinetics, and the use of appropriate disease models. We further provide medicinal chemistry case studies that have addressed one of them to more critically adjust for challenges on our way to therapeutics.