Alzheimer's Disease, the "One-Molecule, One-Target" Paradigm, and the Multitarget Directed Ligand Approach.

No selective drugs exist, and we have been designing, synthesizing, and evaluating multitarget-directed ligands since the beginning of modern medicinal chemistry, without knowing it, most possibly. The challenge to discover the efficient Multi-Target Small Molecules (MTSMs) for Alzheimer's disease (AD) therapy implies to identify the key combination of biological targets to modulate them, thus including in the design the corresponding pharmacophoric groups able to do it. Universal and polyvalent pharmacophoric groups, able to modulate diverse receptors or enzymatic systems, would simplify the drug discovery process leading to new and more efficient MTSMs for AD.