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Journal ArticleDOI

Small-molecule inhibitors of protein–protein interactions: progressing towards the dream

Michelle R. Arkin, +1 more
- 01 Apr 2004 - 
- Vol. 3, Iss: 4, pp 301-317
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TLDR
Here, illustrative examples are used to discuss general strategies for addressing the challenges inherent in the discovery and characterization of small-molecule inhibitors of protein–protein interactions.
Abstract
Protein–protein interactions have a key role in most biological processes, and offer attractive opportunities for therapeutic intervention. Developing small molecules that modulate protein–protein interactions is difficult, owing to issues such as the lack of well-defined binding pockets. Nevertheless, there has been important progress in this endeavour in recent years. Here, we use illustrative examples to discuss general strategies for addressing the challenges inherent in the discovery and characterization of small-molecule inhibitors of protein–protein interactions.

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Citations
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Reaching for high-hanging fruit in drug discovery at protein–protein interfaces

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Intrinsically Disordered Proteins in Human Diseases: Introducing the D2 Concept

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References
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Journal ArticleDOI

In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.

TL;DR: In this article, the authors identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts.
Journal Article

The structure and function

TL;DR: This stately book is to show how the various types of animals have solved the fundamental problems of life, and how their struc-ture is to be interpreted in terms of their functions and environment.
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The Bcl2 family: regulators of the cellular life-or-death switch.

TL;DR: A better understanding of how the Bcl2 family controls caspase activation should result in new, more effective therapeutic approaches in tissue homeostasis and cancer.
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BCL-2 family members and the mitochondria in apoptosis

TL;DR: As the BCL-2 family members reside upstream of irreversible cellular damage and focus much of their efforts at the level of mitochondria, they play a pivotal role in deciding whether a cell will live or die, and it is argued that the amphipathic a-helical BH3 domain serves as a critical death domain in the pro-apoptotic members.
Journal ArticleDOI

Nitric oxide synthases: structure, function and inhibition

TL;DR: This review concentrates on advances in nitric oxide synthase (NOS) structure, function and inhibition made in the last seven years, during which time substantial advances have been made in the authors' understanding of this enzyme family.
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