Exploring skin adverse events and mechanisms of apalutamide using data mining algorithms and network pharmacology

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

Background Skin adverse events of apalutamide pose a major challenge to its clinical use, particularly the severe and difficult identify toxic epidermal necrolysis. For purpose providing basis for monitoring administration further research. This study examined pathways Stephen Johnson Syndrome/Toxic Epidermal Necrolysis using network pharmacology data mining tools analyze skin events. Methods Using Information Component method Reporting Odds Ratio, relationship between was evaluated. Molecular docking utilized explore potential mechanism Syndrome/toxic Results With median time onset all 55 days, total 21 skin-related were found. Low body weight advanced age may be hazards with apalutamide. The results showed substantial association necrolysis, behind this binding JAK1 JAK2. Conclusion Special attention is recommended when apalutamide, especially rapidly progressing To confirm connection triad Janus kinase, events, research required in future.

Language: Английский

In-Depth Understanding of the Structure-Based Reactive Metabolite Formation of Organic Functional Groups

Drug Metabolism Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 43

Published: Feb. 26, 2025

Idiosyncratic drug-induced liver injury (DILI) is a leading cause of drug attrition and/or withdrawal. The formation reactive metabolites widely accepted as key factor contributing to idiosyncratic DILI. Therefore, identifying has become critical focus during lead optimization, and combination GSH-/cyano-trapping cytochrome P450 inactivation studies recommended identify compounds with the potential generate metabolites. Daily dose, clinical indication, detoxication pathways, administration route, treatment duration are most considerations when deprioritizing candidates that Removing structural alerts considered pragmatic strategy for mitigating risk associated metabolites, although this approach may sometimes exclude otherwise potent molecules. In context, an in-depth insight into structure-based metabolite organic functional groups can significantly aid in rational design improved safety profiles. primary goal review delve analysis bioactivation mechanisms their detrimental effects recent examples assist medicinal chemists metabolism scientists designing safer higher likelihood success.

Language: Английский

Research on enhancing enzymatic degradation of anti-digestive peptides containing D-amino acids through N-terminal acetylation

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 158, P. 108337 - 108337

Published: March 3, 2025

Language: Английский