Pharmacophore Modeling of Janus Kinase Inhibitors: Tools for Drug Discovery and Exposition Prediction

Pesticides are essential in agriculture for protecting crops and boosting productivity, but their widespread use may pose significant health risks. Farmworkers face direct exposure through skin contact and inhalation, which may lead to hormonal imbalances, neurological disorders, and elevated cancer risks. Moreover, pesticide residues in food and water may affect surrounding communities. One of the lesser investigated issues is immunotoxicity, mostly because the chronic effects of compound exposure are very complex to study. As a case study, this work utilized pharmacophore modeling and virtual screening to identify pesticides that may inhibit Janus kinases (JAK1, JAK2, JAK3) and tyrosine kinase 2 (TYK2), which are pivotal in immune response regulation, and are associated with cancer development and increased infection susceptibility. We identified 64 potential pesticide candidates, 22 of which have previously been detected in the human body, as confirmed by the Human Metabolome Database. These results underscore the critical need for further research into potential immunotoxic and chronic impacts of the respective pesticides on human health.