| Autor: |
Gabriel Rodrigues Coutinho Pereira, Bárbara de Azevedo Abrahim-Vieira, Joelma Freire de Mesquita |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Pharmaceutics, Vol 15, Iss 4, p 1095 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4923 |
| DOI: |
10.3390/pharmaceutics15041095 |
| Popis: |
Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disorder in adults, which is associated with a highly disabling condition. To date, ALS remains incurable, and the only drugs approved by the FDA for its treatment confer a limited survival benefit. Recently, SOD1 binding ligand 1 (SBL-1) was shown to inhibit in vitro the oxidation of a critical residue for SOD1 aggregation, which is a central event in ALS-related neurodegeneration. In this work, we investigated the interactions between SOD1 wild-type and its most frequent variants, i.e., A4V (NP_000445.1:p.Ala5Val) and D90A (NP_000445.1:p.Asp91Val), with SBL-1 using molecular dynamics (MD) simulations. The pharmacokinetics and toxicological profile of SBL-1 were also characterized in silico. The MD results suggest that the complex SOD1-SBL-1 remains relatively stable and interacts within a close distance during the simulations. This analysis also suggests that the mechanism of action proposed by SBL-1 and its binding affinity to SOD1 may be preserved upon mutations A4V and D90A. The pharmacokinetics and toxicological assessments suggest that SBL-1 has drug-likeness characteristics with low toxicity. Our findings, therefore, suggested that SBL-1 may be a promising strategy to treat ALS based on an unprecedented mechanism, including for patients with these frequent mutations. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
