Frontiers in Clinical Drug Research - Anti-Cancer Agents

Volume: 6

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

Author(s): Aykut Özgür, Lütfi Tutar, Mehmet Gümüş, İrfan Koca, Servet Tunoğlu, Ezgi Nurdan Yenilmez Tunoğlu and Yusuf Tutar

Pp: 109-141 (33)

DOI: 10.2174/9789811478437121060005

* (Excluding Mailing and Handling)

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.


Keywords: Apoptosis, Cancer, Drug design, Oncology, Protein-protein interactions.

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