Influence of Amino Acid Mutations and Small Molecules on Targeted Inhibition of Proteins Involved in Cancer
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
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.Journal Title:
Current Topics in Medicinal Chemistry