12 April 2021
A key focus of the CMD is the development of small molecule chemical probes to investigate the biology of interesting, disease-relevant protein targets. An often touted benefit of probes is that they accelerate the drug discovery process by providing a starting point for small molecule drugs, but is this really the case? This review seeks to answer that question by describing a number of probes that have gone on to inspire a variety of clinical molecules, and will hopefully encourage drug discoverers to turn to chemical probes for inspiration.
24 March 2021
Saracatinib is a clinically-tested dual Src/Abl kinase inhibitor. A new paper from Ellie Williams and the Growth Factor Signalling and Ubiquitination group led by Alex Bullock shows that saracatinib is an equipotent ALK2 kinase inhibitor. The paper outlines preclinical work that supports a current phase 2 clinical trial (NCT04307953) exploring the potential of saracatinib to treat cases of fibrodysplasia ossificans progressiva (FOP) driven by gain of function ALK2 mutations.
26 February 2021
The Kessler group describes a new methodology named ABPP-HT (high-throughput-compatible activity-based protein profiling), implementing a semi-automated proteomic workflow to profile a panel of deubiquitylating enzyme (DUB) inhibitors in cells. This allows direct cellular target engagement of small molecules against cellular DUBs, thereby accelerating DUB drug discovery.
23 February 2021
The Bullock Lab at CMD Oxford were delighted to be a part of this review from LUMC Leiden on Fibrodysplasia ossificans progressiva; an ultrarare congenital disease that progresses through intermittent episodes of bone formation at ectopic sites.
Exscientia and the University of Oxford announce partnership to develop treatments for Alzheimer’s disease
12 February 2021
Neuroinflammation collaboration targeting inflammasome steps-up-the-pace in race for Alzheimer’s disease medicines that alleviate the burden of devastating disease.
ALK2 Receptor Kinase Association with FKBP12.6 Is Structurally Conserved with the ALK2-FKBP12 Complex
1 February 2021
CMD postdoc Ellie Williams has published her structure of the ALK2 receptor kinase bound to FKBP12.6 and dorsomorphin in the journal Biomedicines.
The Bloom syndrome complex senses RPA-coated single-stranded DNA to restart stalled replication forks (new paper published)
29 January 2021
Collaboration between CMD and Andy Blackford's team in @NatureComms describes how the DNA helicase mutated in Bloom syndrome (BLM) interacts with RPA, as well as which functions of BLM are important for the development of cancer.
29 January 2021
When a ribosome stalls during translation, it runs the risk of collision with a trailing ribosome. We have developed a specific small-molecule inhibitor of the deubiquitylase USP9X, linking USP9X with centrosome-associated protein stability Following chemical inhibition of its catalytic activity, levels of Makorins and ZNF598 are diminished, and the ribosomal quality control pathway is impaired. Benedikt Kessler's team at CMD/TDI was part of this study.
11 January 2021
The University of Oxford has joined forces with Thermo Fisher Scientific, the world leader in serving science, to ramp up the university’s capacity to deliver COVID-19 testing data.
Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers (new paper published)
17 December 2020
Loss of WRN, a DNA repair helicase, was identified as a strong vulnerability of microsatellite instable (MSI) cancers, making WRN a promising drug target.
20 November 2020
The Target Enabling Packages (TEPs) Programme continues to elucidate and enable novel targets for drug development.
Structural Biology identifies new information to accelerate structure-based drug design against Covid-19
5 November 2020
A new paper in Nature Communications outlines how an international research team has identified potential ways forward to rapidly design improved and more potent compounds in the fight against COVID-19.
14 October 2020
The Harrington Discovery Institute in the US has announced five winners of its inaugural UK Rare Disease Scholar Award competition.
2 October 2020
The Centre for Medicines Discovery and King Abdulaziz University (KAU) have launched a major collaboration to accelerate medicines discovery using AI technologies, for diseases with unmet need, including rare diseases and cardio-metabolic diseases.
22 September 2020
A large collaborative initiative to contribute to the global anti- COVID-19 effort.
8 September 2020
Joseph Newman has solved a crystal structure of the viral helicase at 1.94 Angstrom resolution (PDB: 6ZSL).
28 July 2020
TargetDB is a tool that aggregates public information available on given target(s) (links to disease, safety, 3D structures, ligandability, novelty, etc.) and assembles it in an easy to read output ready for the researcher to analyse.
28 July 2020
The CMD brings together expertise and capabilities in drug discovery across the Nuffield Department of Medicine.
27 July 2020
The project will last five years and deliver high quality chemical tools that can be used to investigate the biology of disease and discover new targets for drug discovery