Computational prescreening of anticancer drugs prior to in vitro validation, primarily in dogs with exploratory cat data, based on cross-species binding conservation.

Abstract

Advances in veterinary medicine have prolonged the lifespan of companion animals. As a result, the burden of neoplastic diseases has increased. While targeted anticancer drugs are widely used in human oncology, their clinical translation to companion animals remains limited. Therefore, a systematic framework for prioritizing candidate drugs before in vitro or in vivo testing would be a valuable strategy in veterinary medicine. In the present study, we evaluated the cross-species binding potential of FDA-approved targeted anticancer drugs to canine and feline target proteins. Protein sequence analysis revealed high conservation of drug-binding domains between human, dog, and cat target proteins, with average sequence identities of 97.09% in dogs and 99.12% in cats compared with their human counterparts. Computational docking simulations were performed to evaluate the docking scores between selected drugs and their corresponding target proteins in dog and cat. Most selected drug-target complexes exhibited docking scores comparable to those observed for human targets, and cross-species docking-score correlations were high in both dogs (0.988) and cats (0.996). These findings support the use of docking-based prescreening as a rapid candidate-selection strategy prior to in vitro validation in veterinary medicine.