Protein–protein interactions and cancer: small molecules going in for the kill

• Published in: Current opinion in chemical biology Vol. 9; no. 3; pp. 317 - 324
• Main Author: Arkin, Michelle
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2005
• Subjects: Animals; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Humans; Ligands; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - metabolism; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Protein Binding
• ISSN: 1367-5931; 1879-0402
• DOI: 10.1016/j.cbpa.2005.03.001

There has been much progress in the discovery of small, organic molecules that inhibit protein–protein interactions, particularly in the field of cancer. Tubulin polymerization represents a classic target whose function can be allosterically modulated by small molecules. Several protein–protein complexes that regulate apoptosis, or programmed cell death, appear to be particularly amenable to inhibition by small molecules, and recently described compounds have helped to characterize Bcl-2, MDM2 and XIAP as drug targets. Additionally, small-molecule antagonists have recently been described for several new targets, including Rac1–Tiam1, β-catenin–T cell factor (Tcf), and Sur-2–ESX. Not only is the list of protein–protein inhibitors growing, but the inhibitors themselves are moving closer to treating disease.