Effect of Pharmacodynamical Interaction between Nutlin-3a and Aspirin in the Activation of p53 Protein

Abstract

p53, an anti-tumor protein, is a significant protein against cancer suppression. It is controlled by its natural inhibitor, Mdm2 protein. Both p53 and Mdm2 protein exist in the form of a mutual feedback loop so that proper function of p53 protein continues. In various tumors p53 protein is significantly inactivated. This is attributed to the hyper-active levels of its inhibitor. A novel drug, nutlin-3a is used against Mdm2 protein to control its hyper-active level in order to reactivate the function of p53 protein. By far, small molecules of drug nutlin-3a is used as the most promising techniques to reactivate p53 protein. Cancer patients have a high risk of drug-drug interactions (DDI) owing to their multi-dosing prescriptions, which leads them to adverse effects. In the presented work, we have aimed to investigate the effect of pharmacodynamical interaction between two anti-cancer drugs, aspirin and nutlin-3a in the activation of p53 protein. For this purpose, the problem is defined in terms of control system and a ProportionalIntegral-Derivative (PID) controller and an H∞ controller is designed. The comparative performance of both the controllers is analysed by comparing the simulation results achieved. For deep understanding and better results, two different doses of aspirin are used, i.e. a low and a high dose of aspirin. The result achieved through In-Silico trails shows that the hyper-active level of Mdm2 protein is regulated to the desired equilibrium position. However, using a high dose of aspirin acts as input disturbance and leads to undesirable ov