Inhibition of Key Protein-Protein Interactions by Small Molecules for Cancer Drug Design

Pp: 109-141 (33)

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Abstract

SHS investigation development is considered from the geographical and historical viewpoint. 3 stages are described. Within Stage 1 the work was carried out in the Department of the Institute of Chemical Physics in Chernogolovka where the scientific discovery had been made. At Stage 2 the interest to SHS arose in different cities and towns of the former USSR. Within Stage 3 SHS entered the international scene. Now SHS processes and products are being studied in more than 50 countries.

Abstract

Human genome sequencing has revealed the complex nature of the human proteome. Researchers have been focused on mapping the proteome to find the right target for drug design. Inhibition of target proteins may be complemented by redundant forms of the proteins in the pathogenesis of diseases. Therefore, it is important to determine key proteins and their coordinating and/or cooperating partner proteins in protein pathways to design innovative chemotherapeutics. Computational and experimental studies indicated that approximately 200.000 protein-protein interactions (PPIs) have been predicted, with only about 8% identified in humans. PPIs play key roles in many important cellular processes, and especially their up-regulation is closely associated with each step of the tumurogenesis in cancer cells. Therefore, the identification of protein interactions helps researchers to design drugs for target specific cancer treatment. To understand the relations between tumorigenesis and p53- MDM2, c-MYC-MAX, Bcl-2/Bcl-xL, Hsp90-Hsp70, β-catenin-TCF4, and Menin- MLL interactions are an important approach to design specific chemotherapeutics for the treatment of individuals with cancer. This work focuses on key protein interactions on protein signaling pathways and designed inhibitors at these specific junctions in the literature.

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