Alex Eccleston

Senior Editor, Biology at Nature

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Articles

Hinge modifier approach opens door to drugging HECT E3 ligases

4 weeks ago | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 09 May 2025 Ubiquitylation is a vital post-translation modification that controls protein stability, activity and localization and is disrupted in many diseases. Around 650 E3 ubiquitin ligases each recognize a specific set of substrates and are potentially attractive therapeutic targets, but they often lack a confined active-site pocket amenable to small-molecule inhibition. Reporting in Cell, Rothman et al.
Cannabinoid targets hidden pocket for safer pain relief

2 months ago | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 24 March 2025 Non-opioid therapeutics for chronic pain are urgently required, given that opioids lead to dangerous side effects, addiction and tolerance. Agonists of the type 1 cannabinoid receptor (CB1) show promise as alternative analgesics but are still limited by side effects and tolerance. Reporting in Nature, Rangari et al.
Genetics opens new route to degrader discovery

Feb 26, 2025 | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 26 February 2025 Molecular glue degraders are small molecules that promote the interaction of a target protein with an E3 ubiquitin ligase to induce proteasome-mediated degradation. Most glue degraders have been discovered serendipitously, and the paucity of well characterized examples limits their rational discovery as therapeutics.
Peptide blocks phase separation and oncogenic transcription

Feb 5, 2025 | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 05 February 2025 Subcellular assemblies of proteins and nucleic acids termed biomolecular condensates can form by phase separation to compartmentalize biochemical reactions and other processes. Reporting in Nature, Xie et al. show that phase separation of the FOXM1 transcription factor is important for its oncogenic function and is inhibited by AMP-activated protein kinase (AMPK) phosphorylation.
Lipid nanoparticle ferries therapeutic mRNA to the placenta

Jan 7, 2025 | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 07 January 2025 Ionizable lipid nanoparticles (LNPs) that deliver nucleic acid therapeutics to the liver have been successful in the clinic, but achieving LNP delivery to other organs has been challenging. Reporting in Nature, Swingle et al. use a DNA barcoding approach to identify an LNP formulation that delivers therapeutic mRNA to the placenta and alleviates hypertension in mouse models of pre-eclampsia.
Covalent inhibitor engages oncogenic AKT kinase

Dec 2, 2024 | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 03 December 2024 The kinase AKT1 is a key effector of the phosphoinositide 3-kinase signal transduction pathway, which drives cell proliferation and is aberrantly activated in diverse tumours. A study in Nature applies structure-based drug design to develop covalent inhibitors that selectively target an oncogenic AKT1 mutant and avoid the dose-limiting toxicities of pan-AKT inhibitors.
Bivalent molecules unmute silenced genes

Oct 31, 2024 | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 01 November 2024 Small molecule inhibitors of the kinases that regulate gene transcription have potential as anticancer agents but can be toxic in healthy cells. Reporting in Science, Sarott et al. convert a ligand of the transcriptional kinase CDK9 into a bivalent molecule that recruits CDK9 to aberrantly silenced cell death genes in B-cell lymphoma and switches them on.
Agonist antibody lowers blood pressure

Sep 22, 2024 | nature.com | Alex Eccleston

Nature Reviews Drug Discovery (Nat Rev Drug Discov) ISSN 1474-1784 (online) ISSN 1474-1776 (print)
Degrading cell-free DNA to prevent recurrent stroke

Aug 22, 2024 | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 22 August 2024 Stroke associated with atherosclerosis brings a high risk of recurrent vascular events at the early, acute phase. The underlying mechanisms are unclear, and therapies such as statins or aspirin have not been effective. Reporting in Nature, Cao et al. identify an inflammatory pathway activated by cell-free DNA (cfDNA) that induces recurrent stroke in a mouse model. Inhibitors of this pathway prevent recurrent events.
Anti-IL-11 antibody shows anti-ageing properties

Jul 31, 2024 | nature.com | Alex Eccleston

RESEARCH HIGHLIGHT 01 August 2024 Molecular features of ageing include inflammation, cellular senescence and mitochondrial dysfunction, as well as associated defects in signal transduction pathways. A study in Nature demonstrates that blocking the signalling molecule interleukin-11 (IL-11) protects mice from age-associated pathologies and extends their lifespan.