Journal ArticleDOI
Influence of Amino Acid Mutations and Small Molecules on Targeted Inhibition of Proteins Involved in Cancer.
Vishnupriya Kanakaveti,P. Anoosha,Ramasamy Sakthivel,Suresh K. Rayala,M. Michael Gromiha,M. Michael Gromiha +5 more
TLDR
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.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.read more
Citations
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Current progress and future perspectives of polypharmacology : From the view of non-small cell lung cancer
TL;DR: Drug repositioning introduces an affordable and efficient strategy to discover novel drug action, especially when integrated with recent systems biology driven stratagem, in combination with conventional anticancer agents to combat drug resistance in the near future.
Journal ArticleDOI
Forging New Scaffolds from Old: Combining Scaffold Hopping and Hierarchical Virtual Screening for Identifying Novel Bcl-2 Inhibitors.
TL;DR: A novel attempt in terms of blending scaffold hopping and hierarchical virtual screening in order to assess the hybrid method for its efficacy in identifying active lead molecules for emerging PPI target Bcl-2 (B-cell Lymphoma 2).
References
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