In the last century, small-molecule natural products were the main inspiration for most drug
discovery programs based either on high-throughput screening (HTS) or rational design …

Protein–protein interactions have a key role in most biological processes, and offer attractive
opportunities for therapeutic intervention. Developing small molecules that modulate protein …

Abstract p53 is an attractive therapeutic target in oncology because its tumour-suppressor
activity can be stimulated to eradicate tumour cells. Inhibiting the p53–MDM2 interaction is a …

Ubiquitin ligases are well suited to regulate molecular networks that operate on a post-
translational timescale. The F-box family of proteins—which are the substrate-recognition …

Autophagy is a dynamic process of subcellular degradation, which has recently sparked
great interest as it is now recognized to be involved in various developmental processes and …

Key molecular lesions in colorectal and other cancers cause β-catenin-dependent
transactivation of T cell factor (Tcf)-dependent genes. Disruption of this signal represents an …

We have identified a small-molecule inhibitor of tumor necrosis factor α (TNF-α) that
promotes subunit disassembly of this trimeric cytokine family member. The compound …

In this paper, we describe the first prospective application of the shape-comparison program
ROCS (Rapid Overlay of Chemical Structures) to find new scaffolds for small molecule …

Protein–protein interactions (PPIs) control the assembly of multi-protein complexes and,
thus, these contacts have enormous potential as drug targets. However, the field has …

The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant
and contains features essential for coreceptor binding. We determined the structure of V3 in …