The Centre for Medicines Discovery aims to catalyse the discovery and development of new medicines for patients.
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.
Moesin & CD44 are drivers of a co-expression module correlated with pathological/cognitive measures of #Alzheimer’s disease. Developed with @PharmChemBio @EmoryMedicine @UNCPharmacy, this Target Enabling Package opens the way to modulating the CD44:Moesin interaction. #Moesin http://doi.org/10.5281/zenodo.4429216
Chemoproteomic Profiling of Covalent XPO1 Inhibitors to Assess Target Engagement and Selectivity.
Martin JG. et al, (2021), Chembiochem
Assessing the degradation of ancient milk proteins through site-specific deamidation patterns.
Ramsøe A. et al, (2021), Sci Rep, 11
Robotic Catalysis: A High‐Throughput Method for Miniature Screening of Mesoporous Metal Oxides**
Potgieter K. et al, (2021), Chemistry–Methods, 1, 192 - 200