Computational approaches to the design of novel 5-HT6R ligands

5-Hydroxytryptamine (5-HT, serotonin) subtype 6 receptor (5-HT6 receptor, 5-HT6R) belongs to a 5-HT subclass of a relatively wide G protein-coupled receptor (GPCR) family. Accumulated biological data indicate that 5-HT6R antagonists and agonists have a great potential for the treatment of neuropathological disorders, such as Parkinson's disease, Alzheimer's disease, and schizophrenia. A number of painstaking efforts have been made toward the design of novel 5-HT6R ligands; however, there are still no drugs that successfully passed all the clinical trials and entered the market, except for several multimodal ligands. Novel active molecules are strongly needed to progress this development forward. The in silico drug design has some benefits compared with the other rough approaches in terms of thoroughness and predictive accuracy; therefore, it can be effectively used as a solid foundation for the design of novel 5-HT6R ligands with high potency and selectivity. Here, we provide an overview of the reported computational approaches to the design of novel 5-HT6R ligands.