Journal Article

Computational approaches to the design of novel 5-HT6 R ligands

Veselov, Mark S., Majouga, Alexander G., Ivanenkov, Yan A., Filkov, Gleb I., Baranovsky, Sergey S., Chufarova, Nina V.

2014

Overview

5-Hydroxytryptamine (5-HT, serotonin) subtype 6 receptor (5-HT receptor, 5-HT R) belongs to a 5-HT subclass of a relatively wide G protein-coupled receptor (GPCR) family. Accumulated biological data indicate that 5-HT R 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-HT R 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 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-HT R ligands with high potency and selectivity. Here, we provide an overview of the reported computational approaches to the design of novel 5-HT R ligands.

• Publisher: De Gruyter
• Subject: Animals / antagonists / Central Nervous System Diseases - drug therapy / Computer Simulation / Computer-Aided Design / docking / Drug Design / Humans / Ligands / Mental Disorders - drug therapy / pharmacophore / QSAR / Receptors, Serotonin - chemistry / Receptors, Serotonin - metabolism / Serotonin Agents - chemistry / Serotonin Agents - pharmacology / Serotonin Agents - therapeutic use