Screening and Repositioning of the Drugs That Possess Binding Affinity towards Notch 1 Receptor Thereby Inhibiting Cell Proliferation in Leukaemia

Cancer is one of the life threatening disease of 20th century and spreading further with increasing incidence in 21st century. Leukemia’s are the type cancers of bone marrow and blood mostly identified in adolescent and young adult population. They are also challenges regarding the effective delivery of the therapy specific to the adolescent and young adult group. Signalling pathways have been investigated for their role in cancer pathogenesis. Notch receptors may contribute to malignancies as both oncogenes and suppressors. The dysregulation of the notch receptor signalling pathway has been associated with disorders, including cancers. The main focus of this research was on notch 1 receptor which has maximum contribution in suppressing leukemia. In activation of notch 1 receptors to gain a function, mutations were identified in more than 50% of T-ALL cases. Gamma secretase inhibitors were first tested small molecule drug candidates to block the signalling of notch receptors. Furthermore, monoclonal antibodies. However they have been challenging in clinical trials due to primary resistance/dose limiting on target toxicities. Success in targeting these receptors could be achieved by repositioning the drugs -where we investigate the effective method to identify new indications of existing medications, which failed to show much therapeutic benefits. The drug bank database was used as a resource for the pharmacological and molecular information of the compound to facilitate the discovery, screening and the prediction of binding interactions of the candidate drug and its analogues.

Author(s): Mary Manisha Mannam*, Bantupalli Nookiah Dora, Mohammed Ismail Lunat and Mandurval Abdul Hakeem

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