Current Challenges and Opportunities in Designing Protein-Protein Interaction Targeted Drugs

Advances and Applications in Bioinformatics and Chemistry : AABC
Woong-Hee ShinZiyun Ding

Abstract

It has been noticed that the efficiency of drug development has been decreasing in the past few decades. To overcome the situation, protein-protein interactions (PPIs) have been identified as new drug targets as early as 2000. PPIs are more abundant in human cells than single proteins and play numerous important roles in cellular processes including diseases. However, PPIs have very different physicochemical features from the conventional drug targets, which make targeting PPIs challenging. Therefore, as of now, only a small number of PPI inhibitors have been approved or progressed to a stage of clinical trial. In this article, we first overview previous works that analyzed differences between PPIs with PPI targeting ligands and conventional drugs with their binding pockets. Then, we constructed an up-to-date list of PPI targeting drugs that have been approved or are currently under clinical trial and have bound drug-target structures available. Using the dataset, we analyzed the PPIs and their ligands using several scores of druggability. Druggability scores showed that PPI sites and their drugs targeting PPIs are less druggable than conventional binding pockets and drugs, which also indicates that PPI drugs do not follow the ...Continue Reading

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Methods Mentioned

BETA
X-ray

Software Mentioned

FTMap
ChEMBL
SiteScore
QED
SiteMap
SiteFinder
Quantitative Estimate of Druglikeness ( QED )
PubChem
Abciximab

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