Las reacciones cruzadas de fármacos (ADR o RAMs) son efectos no deseados de un fármaco, que se producen por la no especificidad de este hacia su diana, debido a que la estructura química no se correlaciona con su proceso definido. Las RAMs representan una amenaza para la salud porque los fármacos se unen a receptores para los que no están diseñados, activándolos produciendo daños al activar cascadas de reacciones no deseadas. El presente trabajo tiene como objetivo identificar reacciones cruzadas de fármacos en un paqeute de datos de 921 fármacos aceptados por Food and Drug Administracion (FDA), utilizando herramientas computacionales para analizarlos. La etapa in silico se inició con MolShaCS el cual presenta la capacidad de identificación de potenciales de interacciones cruzadas entre fármacos, los resultados en extensión .dat fueron usados como imput por Radatools 3.2 (R...

Objective: Patients with non-small cell lung cancer positive for the anaplastic lymphoma kinase (ALK+) gene mutation who also have mutations in the Kirsten rat sarcoma (KRAS) gene, such as KRAS G12C, are showing resistance to both anaplastic lymphoma kinase (ALK) gene and KRAS inhibitors. Therefore, the interaction between ALK inhibitors and KRAS was analyzed to suggest a synergy between them. Materials and methods: The study performed homology modeling of the KRASwt, KRAS G12C and ALKwt structures. Subsequently, molecular dockings were carried out to determine the binding energy of ALK and KRAS inhibitors and to evaluate the possible interaction of ALK inhibitors with KRAS and the KRAS G12C structure. Finally, the expression in the RAS/MEK pathway was analyzed using the Western Blot technique. Results: The binding energy values show the potential interaction of ALKwt inhibitors, such as...

Objective: PI3K is one of the most frequently mutated proteins in cancer, resulting in changes to its functions in regulating metabolism, immunity, among others. Despite the identification of specific drugs targeting PI3K, significant resistance tothese therapies has been observed. Therefore, the search for new inhibitors is crucial. This project proposes a strategy based on in silico computational tools for screening Food and Drug Administration (FDA)-approved drugs, aiming to evaluate their potential for drug repositioning. Materials and methods: This study obtained the sequence of PI3Kα from UniProt Knowledgebase and its three-dimensional structure from AlphaFold Protein Structure Database, which were then coupled with adenosine triphosphate (ATP) and its selective inhibitors: inavolisib, taselisib, CH5132799, alpelisib and ZSTK474. Drug-protein interaction analysiswas performed usin...

Objective: To describe the behavior of the BCL-2 protein in non-small-cell lung cancer cell models in response to treatment with ALK (anaplastic lymphoma kinase) protein tyrosine kinase inhibitors (crizotinib and alectinib) and their potential dual BCL-2-ALK inhibition. Materials and methods: Three non-small-cell-lung cancer cell models were used: Ba/f3 EML4-ALKWT, Ba/f3 EML4-ALKL1196M and Ba/f3 EML4-ALKG1202R, generated by site-directed mutagenesis. These were treated with crizotinib and alectinib in a dose-responsive manner, and an apoptosis assay was also conducted to confirm pharmacological susceptibility. Subsequently, BCL-2 protein expression was measured under three treatment conditions (no treatment, 100 nM crizotinib and 50 nM alectinib). Finally, a search for BCL-2 and ALK ligands was performed for molecular docking simulation and interaction energy calculation, measured in kca...