Background. The search for promising nonsteroidal anti-inflammatory drugs (NSAIDs) is aimed, in particular, at identifying molecules with multitargeted anti-inflammatory and analgesic effects (including through central mechanisms).

Objective: To study the interactions of a candidate NSAID molecule (SV-1010) with opioid receptors and compare them with the effects of known agonist molecules (butorphanol and U-50488) using chemoreactomic analysis and docking.

Material and methods. Chemoreactomic analysis of NSAID mechanisms of action was conducted in three stages: data sampling, establishment of lists of molecules with known properties, and calculation of Kd binding constants and EC50 activation constants. Docking of kappa opioid receptors was performed using MarvinSketch, MOPAC2012, and AutoDock Vina. A comparison of the results of chemoreactomic modeling and docking was performed.

Results. Chemoreactomic analysis of the interactions of the studied molecules with opioid receptors showed that the median and average values ​​of the binding constants Kd of the SV-1010 compound are comparable with the estimates of the constants obtained for butorphanol and U-50488 (75–98 nM for delta receptors, 62–81 nM for kappa receptors, 198–244 nM for mu receptors). Among the studied opioid receptor subtypes, the lowest Kd values ​​were established for SV-1010 for kappa receptors (64.8±46.3 nM; delta and mu receptors: 79.9±77.6 and 243.8±246.9 nM, respectively). No significant difference in the binding of SV-1010 molecules to kappa-1 and kappa-2 opioid receptors was detected (Kd in the range of 23.7–54.5 nM). Docking of the studied molecules into the structure of the human kappa receptor allowed us to obtain Kd values ​​and formulate the mechanism of binding of SV-1010 to the kappa-opioid receptor site (potentially, the key binding amino acids of the kappa-opioid receptor site are ILE730, VAL667, MET579, ILE726, TRP723, ILE460 and TYR464). A comparison of the results of chemoreactomic modeling and docking made it possible to find a correlation expressed by the equation “35.8x – 4790” with a correlation coefficient close to unity. The results of chemoreactome modeling of EC50 constants confirmed the results of the Kd binding constant analysis, including the finding that SV-1010 exhibits greater affinity for kappa receptors than for mu receptors.

Conclusion. Chemoreactomic and docking modeling of the SV-1010 molecule's effects support the hypothesis that this compound may be a kappa-opioid receptor agonist, indicating the potential for experimental and other studies of SV-1010 with a focus on kappa-opioid receptors.