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Lung cancer is the world's most prevalent disease leading to several fatalities. An enormous amount of effort has been made to increase the disease-free survival rate, in this screening study for early diagnosis therapy. In this study, the selected hypothetical proteins of E3 ubiquitin ligase involved in lung cancer were studied. The sequence and structural annotations were determined by ExpasyProtParam and SOPMA software. The structural three-dimensional (3D) of these proteins were predicted through homology modeling using swiss-modeller. The natural compound inhibitors like piperine and curcumin were studied for binding mechanisms and pharmacokinetic analysis. The natural inhibitor piperine has the highest binding affinity towards the A0A0A8K9F1 hypothetical protein.