Chimeric molecule for targeting c-MYC in cells

Abstract

Disclosed herein are chimeric fusion proteins comprising a c-Myc inhibitor fused to genetically modified Pseudomonas Aeruginosa Exotoxin A ('tPE'), said fusion proteins being capable of penetrating anucleus of a cell and inhibiting c-Myc activity within the nucleus. In particular, the tPE comprises PE Domains la and I I, and the c-Myc inhibitor is H1 peptide derived from helix 1 carboxylic regionof c-Myc. Also disclosed herein are pharmaceutical compositions comprising chimeric fusion proteins, methods of delivering, methods of preparing, and use of chimeric fusion proteins to prevent or treat a c-Myc dependent cancer.

Description

[0001] This application claims the benefit of Singapore Provisional Application No. 10201709898X filed on 29 November 2017, the contents of which are hereby incorporated by reference in their entirety. technical field [0002] The present invention relates to the field of cancer, and more particularly, to compositions and methods for treating cancer using chimeric fusion proteins comprising genetically modified Pseudomonas aeruginosa fused to a c-Myc inhibitor Exotoxin A, the c-Myc inhibitor can target and penetrate the nucleus, and inhibit the activity of the transcription factor c-Myc in the nucleus. Background technique [0003] c-myc is a regulatory gene encoding the transcription factor c-Myc. Mutated forms of c-Myc are found in many cancers, which lead to constitutive expression of c-Myc and display oncogenic activity. This leads to dysregulation of the expression of many genes, some of which are involved in cell proliferation, and lead to the formation of cancer. ...

AI Technical Summary

Problems solved by technology

[0005] Therefore, there is an unmet need for methods of detecting and / or targeting c-Myc in cells

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