Virtual Screening of Selective Cyclooxygenase-2 Inhibitors with Low Cardiovascular Disease Risk
Objective:To find selective Cyclooxygenase-2(COX-2)inhibitors with thromboxane A2 receptor(TP)inhibition with the aim of reducing their cardiovascular disease risk.Method(s):In this study,a total of 512 TP inhibitors were obtained from public databases.Through molecular docking,molecular dynamics simulation,and ADMET prediction,a compound named TP84 was identified.Result(s):The molecular docking results demonstrate that TP84 exhibits higher affinity for COX-2 and lower affinity for Cyclooxygenase-1(COX-1)compared with rofecoxib,a previously approved selective COX-2 inhibitor.Furthermore,molecular dynamics simulation reveals that TP84 binds unstably to COX-1 during simulations,whereas TP84 can bind COX-2 stably.The binding free energy of TP84 to COX-2 was three times higher than that of COX-1.Furthermore,the medicinal chemistry,absorption,distribution,metabolism,excretion and toxicological properties of TP84 are predicted by ADMET to be within the acceptable range for drug-like candidates.Conclusion(s):TP84 is a potential selective COX-2 inhibitor drug with low cardiovascular disease risk.
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