Centre for Synthetic Biology and the Bioeconomy

Staff Profile

Professor Mike Waring

Chair of Medicinal Chemistry

Background

Scopus ID: 7102782045; ORCID ID: 0000-0002-9110-8783 


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Roles and Responsibilities

Mike's research interests are concerned with drug discovery using medicinal chemistry. He is Head of Medicinal Chemistry in the Cancer Research UK Newcastle Drug Discovery Group and Director of Academic Medicinal Chemistry for Cancer Research Horizons, CRUK's innovative organisation for therapeutic discovery. He is the Director of the EPSRC Centre for Doctoral Training in Molecular Sciences for Medicine and Editor-in-Chief of RSC Medicinal Chemistry.

Mike teaches Pharmacokinetics and Drug Metabolism in the Chemistry with Medicinal Chemistry (BSc and MChem) and Drug Chemistry (MSc) degree programmes.

Awards and Esteem

2022 European Federation of Medicinal Chemistry UCB-Ehrlich Prize

for excellence in medicinal chemistry

2018 American Chemical Society Hero of Chemistry

for the discovery of the mutant EGFR inhibitor osimertinib (Tagrisso), a treatment for resistant forms of non-small cell lung cancer.

2017 Royal Society of Chemistry Malcolm Campbell Medal

for excellence in biological and medicinal chemistry.

2017 Elected Fellow of the Royal Society of Chemistry

2014 Royal Society of Chemistry Inaugural Biological and Medicinal Chemistry Sector Lectureship

in recognition of outstanding contributions to medicinal chemistry.

2010 Royal Society of Chemistry Capps Green Zomaya Memorial Medal

for outstanding contributions to medicinal chemistry and outstanding success in bringing medicines to the clinic.

2010 European Federation of Medicinal Chemistry Prize

for an outstanding young medicinal chemist in industry (runner up).

Qualifications

BSc(Hons), First Class, in Chemistry 1996 (University of Manchester)

PhD in Organic Chemistry 1999 (University of Manchester) with Prof. T. J. Donohoe

Previous Positions

April 2011 – August 2015: Principal Scientist in Medicinal Chemistry at AstraZeneca, Alderley Park, UK.

July 2001 – March 2011: Team Leader in Medicinal Chemistry at AstraZeneca, Alderley Park, UK

January 2000 - July 2001: Post-doctoral researcher in the group of Prof. P. D. Magnus, University of Texas at Austin, USA.

 

Research

Anti-cancer drug discovery

Within the Cancer Research UK Newcastle Drug Discovery Programme, we run a portfolio projects focused on identifying new molecules for novel cancer targets in areas of unmet medical need. We focus particularly on treatments for drug resistant cancers and to high value challenging targets such as protein-protein interactions. These projects involve cutting-edge structure based drug design and employ modern methods for hit generation and optimisation. In particular, we focus on fragment-based lead generation, DNA-encoded libraries and covalent inhibition.

Our group is part of Cancer Research Horizons Therapeutic Innovation, Cancer Research UK's national innovation engine. Part of our portfolio is run collaboration with Astex Pharmaceuticals through a strategic drug discovery alliance.

New methods of hit generation and lead optimisation

The identification of small-molecule ligands for protein targets remains a slow step in the medicinal chemistry and chemical biology fields. We are interested in developing new methods for hit generation and optimisation, which could be applied generally to make this process more successful by developing new technologies for finding hits and faster, more effective ways to optimise them. We are also interested in developing new chemical modalities that could lead to drugs for traditionally intractable targets.

Fraglites

In the group, we have developed FragLites, a set of small, halogenated probes that allow mapping of druggable sites on proteins and allow de novo hit generation. These compounds are now routinely employed in our projects and are becoming widely adopted in hit finding.

Published examples have shown how this approach can lead to novel inhibitors of CDK2, including the identification of allosteric binding sites and can differentiate the druggability of bromodomains BRD4 and ATAD2.

DNA-encoded libraries

We now employ DNA-encoded approaches to hit generation and lead optimisation using novel chemistry that we have developed in the group. In particular, our chemistry uses micellar catalysis as a way of carrying out highly efficient on-DNA chemistry and allows the construction of DNA-encoded libraries of the highest fidelity.

Thus far, we have developed Suzuki, amide, Buchwald, Sonogashira, Heck, SNAr and hydrogenation reactions on DNA. We have synthesised libraries exceeding 500,000 encoded compounds to date.

These libraries are being screened for start points for drug discover in cancer, neurological and metabolic disorders.

We are also applying DNA-encoded methods to later stages of drug discovery such as fragment optimisation, with the potential to rapidly accelerate the discovery of new drugs.

Diversity-oriented synthesis

We are developing diversity-oriented methods for the synthesis of lead-like screening libraries, in particular using our Build-Couple-Transform paradigm for introducing scaffold diversity. This technology is used to find start points for novel drug targets.

Covalent inhibition

Covalent inhibition represents a highly attractive approach to new medicines through targeting proteins with irreversible binding. We are developing covalent inhibitors for therapeutic targets with novel warheads. This approach involves introduction of covalent warheads to existing scaffolds and development of inhibitors from covalent fragments.

Funding

Our Research is funded by Cancer Research UK, Pancreatic Cancer Research Fund, EPSRC, Wellcome Trust, Astex Pharmaceuticals, AstraZeneca, Genentech, Pharmaron, Exscientia and Newcastle University. We are very grateful for their generous support. Funded opportunities will be advertised when available.

Teaching

CHY3109/3110/8822 - Stage 3 Medicinal Chemistry - Drug Metabolism and Toxicology.

Publications