Efficacy and Toxicity Assessment of Different Clinically Used Small Molecular Tyrosine Kinase Inhibitors by Computational Molecular Docking Method

Along with the antibody based antiangiogenic (AAG) drugs, several small molecular antiangiogenic (sAAG) drugs are also in clinical practice for the treatment of different cancers. Though population based clinical trials have provided their efficacy; however, comparative efficacies of these drugs at molecular level are not available. The drug-target network is highly important to understand the efficacy and toxicity of drugs in terms of systems biology. In this study, multiply molecular docking between several sAAG drugs and different target receptors are carried out. Our data suggest that though gefitinib is quite potent in targeting different receptors involved in angigiogenesis, but it may impose some serious side effects within physiological system. Our data also suggest that one sAAG drug have some preferential binding affinity to one receptor while have lower binding capacity for other receptor. Hence different sAAG drugs may produce different types of toxicity within the physiological system. For example, lapatinib has highest binding affinity towards NO synthease, while erlotinib has lowest binding affinity to this enzyme. Similarly, sunitinib has highest binding affinity towards beta-2 receptor, while lapatinib has lowest affinity to this receptor.