Abstract

Insilico designing and development of potent drug inhibitor to MDM2 protein in cancer through molecular docking studies

Author(s): Pravallika vadlamudi, Manas Ranjan Barik

Cancer is a class of diseases characterized by out-of-control cell growth. Cancer is a leading cause of death worldwide.The p53 tumor suppressor is one of the principal mediators of cell-cycle arrest and the activation of apoptosis in response to cellular injuries . In normal unstressed cells, p53 is regulated by a feedback loop with the negative regulator protein MDM2 (murine double -minute clone 2, referred to as human double –minute clone 2, HDM2 , in humans) . A well -known mechanism for the loss of wild –type p53 activity in cancer cells is the overexpression of MDM2.The murine double minute 2 (MDM2) protein facilitates G1 to S phase transition by activation of E2F-1 and can enhance cell survival by suppressing wild-type p53 function.Murine DM2 (MDM2) protein is overexpressed in a variety of neoplasms, including acute leukemias, myelodysplastic syndrome, chronic lymphocytic leukemia and lymphomas , multiple myelomas etc. Blocking the MDM2-p53 interaction to reactivate the p53 function is a promising cancer therapeutic strategy. Activation of the p53 protein protects the organism against the propagation of cells that carry damaged DNA with potentially oncogenic mutations. This can be attained by designing a molecule which can bind to P53 transactivation site of Mdm2 and further this Mdm2 protein cannot bind with P53 .The aim of present study is designing a small molecule(antagonist) having capability to bind with the over expressed Mdm2 protein and blocking its path to bind with p53 tumour suppressor protein that is having sufficient absorption and free of hepatotoxicity and carcinogenicity.

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