Influence of Amino Acid Mutations and Small Molecules on Targeted Inhibition of Proteins Involved in Cancer

Author(s): V. Kanakaveti, P. Anoosha, R. Sakthivel, S.K. Rayala, M.M. Gromiha*

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 6 , 2019

DOI : 10.2174/1568026619666190304143354

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Graphical Abstract:


Abstract:

Background: Protein-protein interactions (PPIs) are of crucial importance in regulating the biological processes of cells both in normal and diseased conditions. Significant progress has been made in targeting PPIs using small molecules and achieved promising results. However, PPI drug discovery should be further accelerated with better understanding of chemical space along with various functional aspects.

Objective: In this review, we focus on the advancements in computational research for targeted inhibition of protein-protein interactions involved in cancer.

Methods: Here, we mainly focused on two aspects: (i) understanding the key roles of amino acid mutations in epidermal growth factor receptor (EGFR) as well as mutation-specific inhibitors and (ii) design of small molecule inhibitors for Bcl-2 to disrupt PPIs.

Results: The paradigm of PPI inhibition to date reflect the certainty that inclination towards novel and versatile strategies enormously dictate the success of PPI inhibition. As the chemical space highly differs from the normal drug like compounds the lead optimization process has to be given the utmost priority to ensure the clinical success. Here, we provided a broader perspective on effect of mutations in oncogene EGFR connected to Bcl-2 PPIs and focused on the potential challenges.

Conclusion: Understanding and bridging mutations and altered PPIs will provide insights into the alarming signals leading to massive malfunctioning of a biological system in various diseases. Finding rational elucidations from a pharmaceutical stand point will presumably broaden the horizons in future.

Keywords: EGFR, Bcl-2, Protein-protein interactions, Drug targets, Mutation, Cancer.

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VOLUME: 19
ISSUE: 6
Year: 2019
Published on: 02 May, 2019
Page: [457 - 466]
Pages: 10
DOI: 10.2174/1568026619666190304143354
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