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News

Unexpected structural mimicry of a molecular glue drug and cancer mutants

Neomorphic cancer mutations and drug UM171 both induce LSD1-CoREST-HDAC1/2 degradation via the E3 ligase KBTBD4. The Bullock group reveals how the mutations and UM171 similarly remodel the KBTBD4 surface to recruit neosubstrate HDAC1/2, showing how genetic mutations can mimick a molecular glue drug.

Robotic hands holding a red pill that is breaking apart into 0s and 1s

AI in Alzheimer’s disease drug discovery

The ODDI has been featured in a Wall Street Journal article, describing the use of AI in identifying and stratifying novel targets for therapeutic intervention in Alzheimer’s disease.

Dr Daniel Ebner in the lab

Centre for Medicines Discovery raising awareness and funding for GBM research

Georgie Maynard, together with her brother Charlie Maynard - Liberal Democrat MP for Witney, visited the Centre for Medicines Discovery at Oxford University and the Brain Tumour Charity/CRUK funded research team led by Prof Daniel Ebner working on a five-year study to identify existing cancer drugs that might be able to shrink brain tumours.

CMD study identifies potent binders of the transcription factor Brachyury

A new study from the Newman group at CMD, working together with the groups of Paul Workman at the Institute of Cancer Research and David Drewry at the Structural Genomics Consortium University of North Carolina have identified potent ligands of the transcription factor Brachyury that may be developed into degraders for cancer therapy.

Cancer researcher in a lab looking into a microscope

Researchers discover new way to target cancer and immune-related diseases

Groundbreaking research by scientists from the Centre for Medicines Discovery at the Nuffield Department of Medicine opens up new possibilities for developing treatments that could both fight cancer and regulate the immune system, offering hope for better and more precise therapies in the future.

IMPRESA team, Research Informatics Facility, Centre for Medicines Discovery (CMD), University of Oxford

IMPRESA showcased at Oxford Digital Festival 2024

The Research Informatics Facility introduced IMPRESA at the Oxford Digital Festival 2024, showcasing its integration of workflows, receiving feedback from attendees and exploring new opportunities.

Male scientist in a lab

Researchers discover the enzymatic mechanism for human ceramide synthase

In an exciting collaboration between academia and industry, researchers at NDM’s Centre for Medicines Discovery and Boehringer Ingelheim have discovered the reaction mechanism for human ceramide synthase (CerS), which could help to form CerS-inhibiting products in the future.

New potent and selective tetrahydroisoquinoline-based KEAP1 inhibitors

KEAP1 is a therapeutic target for conditions of inflammation and oxidative stress. The Bullock group have collaborated with Anders Bach (Copenhagen) on a new paper describing potent and selective tetrahydroisoquinoline-based inhibitors of KEAP1.

New CMD publication reveals multidomain KCTD1 structure and effects of mutation

Mutations in the BTB family protein KCTD1 disrupt its binding to transcriptional repressor TFAP2 causing scalp-ear-nipple syndrome. A new study by the Bullock group at CMD Oxford reports how a BTB extension and ion-binding domain contribute to this pentameric assembly and TFAP2 interaction.

What's next for Alzheimer's Disease

Inside Health reports on the latest advances in treating Alzheimer's disease, and the therapies being developed

Activation of SYK, a kinase implicated in Alzheimer’s disease

Publication explores the mechanism of activation of SYK upon phospho-ITAM binding through structures and biophysical measurements

Beyond lecanemab: unravelling the future of Alzheimer’s treatments

The latest Alzheimer’s treatments work by removing the build-up of a protein in the brain, called amyloid. But is this the only way we will treat the disease in the future?

First structure of amino acid transporter and viral receptor CAT1 determined at the CMD

Cationic Amino acid Transporter 1 (CAT1) imports basic amino acids and is also the receptor of two retroviruses. Our new structures of MmCAT1 reveal its amino acid selectivity, transport, and interactions with Friend Murine Leukemia Virus.

CMD study reports first chemical probe for CDKL2

Cyclin-dependent kinase-like 2 (CDKL2) is a serine/threonine kinase with reported links to development and cancer. A new study involving collaboration between the Bullock group at CMD Oxford and Alison Axtman at SGC-UNC reports the first chemical probe for CDKL2 providing an important reagent to interrogate CDKL2-dependent biology.

DPhil student Donna Di Rienzo is the recipient of an ARUK Thames Valley Pilot Project Award

This grant will launch an exciting collaboration with Dr Darragh O’Brien, Head of Structural and Mechanistic Proteomics, to run a ubiquitomic study to identify novel substrates of the E3 ligase IDOL, which is a promising therapeutic target for Alzheimer’s disease.

Matthew Holland boat race

DPhil Student Matthew Holland Featured in Tatler Magazine after Presenting The Boat Race on BBC One

He finds parallels between explaining science and rowing. Both may seem complex at first, but breaking down basic principles can simplify understanding.

NLRP3

NLRP3 Inflammasome “DUBbed” by UCH-L1, affecting IL-1β production macrophages and microglia

Activation of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome complex involves association with ubiquitin C-terminal hydrolase 1 (UCH-L1). UCH-L1 chemical inhibition and deletion interfere with NLRP3 assembly and IL-1β production in macrophages and microglia.

Ibrutinb NUDT5 NUDT14

CMD Study Discovers Unexpected Noncovalent Off-Targets of Clinical BTK Inhibitors

BTK inhibitors are a cornerstone of clinical anticancer therapy thanks to their strong and sustained effect on key disease-driving oncogenes. A new study by the Huber lab in collaboration with the Brennan and Fedorov groups at CMD, as well as Ivan Ahel’s lab at the William Dunn School at Oxford, reveals that these drugs exhibit unexpected off-target activity against non-kinase proteins that is independent of their reactive warhead.

ALK2 Inhibitors

Discovery of Conformationally Constrained ALK2 Inhibitors

The Bullock's lab, in collaboration with Ontario Institute for Cancer Research (OICR) and M4K Pharma, has published a study in the Journal of Medicinal Chemistry about the discovery of conformationally constrained ALK2 inhibitors.

The Cancer Grand Challenges PROTECT team

Research team receives $25m Cancer Grand Challenges award

A global, interdisciplinary team of researchers, including the Centre for Medicines Discovery’s Professor Frank von Delft, has been selected to receive a Cancer Grand Challenges award of up to $25m over five years to tackle the solid tumours in children challenge. The Cancer Grand Challenges PROTECT team is led by Professor Stefan Pfister of the Hopp Children's Cancer Center in Heidelberg.

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