In silico identification of multi-target ligands for neurodegenerative diseases drug development
November 2022
Bulgarian Academy of Sciences, Sofia, Bulgaria
The conventional treatment of neurodegenerative diseases (NDDs) is based on the “one molecule—one target” paradigm. To combat the multifactorial nature of NDDs, the focus is now shifted toward the development of small-molecule-based compounds that can modulate more than one protein target, known as “multi-target-directed ligands” (MTDLs), while having low affinity for proteins that are irrelevant for the therapy. In this study, more than 650,000 compounds were screened by a series of in silico approaches to identify drug-like compounds with predicted activity simultaneously towards three important proteins in the NDDs symptomatic treatment. Four selected hits underwent subsequent refinement through in silico blood-brain barrier penetration estimation, safety evaluation, and molecular dynamics simulations, resulting in two hit compounds that constitute a rational basis for further development of multi-target active compounds against NDDs.
In silico identification of multi-target ligands as promising hit compounds for neurodegenerative diseases drug development
Ivanka Tsakovska, Nikolay T. Tzvetkov
Added on: 11-28-2022
[1] https://www.mdpi.com/1422-0067/23/21/13650
