doi.bio/miles_congreve

Miles Congreve

Early Life and Education

Miles Congreve obtained a Bachelor of Science (BSc) in Biological Chemistry from the University of Leicester in 1990. He then pursued a PhD in Chemistry at the University of Cambridge from 1990 to 1993.

Career

Congreve has extensive experience in the pharmaceutical industry, with a focus on drug discovery and chemistry. He began his career at GlaxoSmithKline in 1993, leading a team that developed innovative chemistry technology.

In July 2001, Congreve joined Astex Therapeutics as the Director of Chemistry, where he established and managed a chemistry team specializing in Fragment-Based Drug Discovery and structure-based drug design. During his time at Astex, Congreve co-authored several publications, including:

• "A novel phase-switching protecting group for multi-step parallel solution phase synthesis"
• "The Application of Quantitative Analytical Constructs for Chemistry Optimization, Monomer Rehearsal and Reactivity Prediction in Solid Phase Library Synthesis"
• "Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B"
• "Versatile solid-phase synthesis of secondary amines from alcohols. Development of an N-Boc-(o-nitrobenzene) sulfonamide linker"
• "Analytical Techniques for Small Molecule Solid Phase Synthesis"

In September 2008, Congreve moved to Sosei Heptares as the Chief Scientific Officer, overseeing the development and implementation of structure-based drug design approaches for GPCR targets. He held various positions at Sosei Heptares, including VP Chemistry, SVP Drug Discovery, and finally CSO. Some of his notable contributions during this period include:

• "Structure-Based Optimization Strategies for G Protein-Coupled Receptor (GPCR) Allosteric Modulators: A Case Study from Analyses of New Metabotropic Glutamate Receptor 5 (mGlu5) X-ray Structures"
• "Advances and Insights from CNS G Protein-Coupled Receptor Crystallography"
• "Structure-based Drug Discovery and Advances in Protein Receptor Crystallography"
• "Ask the Experts: Past, present and future of the rule of five"
• "Imidazopyridine derivatives as inhibitors of receptor tyrosine kinases"

In 2022, Congreve joined Isomorphic Labs as the Chief Scientific Officer, where he currently leads the scientific research and development efforts.

Research Interests and Publications

Congreve's research interests lie primarily in the field of drug discovery and Fragment-based lead discovery. He has co-authored numerous publications in prestigious journals such as "Drug Discovery Today", "Nature Reviews Drug Discovery", and the "Journal of Medicinal Chemistry". Some of his most influential papers include:

• "Fragment-based lead discovery" (2004) - This paper highlights the advantages of fragment-based approaches in drug discovery, including the need for fewer compounds to be screened and synthesized, and a high success rate in generating chemical series with lead-like properties.
• "Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B" (2003) - This paper reports the crystal structures of regulatory sulphenic and irreversible sulphinic and sulphonic acids of protein tyrosine phosphatase 1B (PTP1B), which is a crucial enzyme in the negative regulation of the insulin receptor.
• "A 'rule of three' for fragment-based lead discovery?" (2003) - This work proposes a set of parameters to determine drug-likeness for oral delivery, including the number of hydrogen bond donors and acceptors, molecular weight, and lipophilicity.
• "Fragment-based lead discovery: leads by design" (2005) - This publication discusses the benefits of fragment-based lead discovery in identifying simpler and less functionalized compounds with high 'ligand efficiency', making them suitable for optimization into clinical candidates.

Affiliations

Throughout his career, Congreve has been affiliated with the following institutions:

• University of Hertfordshire
• University of Cambridge
• AstraZeneca
• Astex
• Sosei Heptares

- Isomorphic Labs

Miles Congreve

Chief Scientific Officer at Isomorphic Labs

Miles Congreve is a researcher in medicinal and pharmaceutical chemistry with a BSc in biological chemistry from the University of Leicester and a PhD in synthetic chemistry from the University of Cambridge. He is currently Chief Scientific Officer at Isomorphic Labs and was previously Head of Chemistry at Heptares from 2008. Congreve has also previously worked at Astex Pharmaceuticals (now Astex Therapeutics, part of Otsuka) and Glaxo.

Research Focus

Congreve's research focuses on drug discovery and receptors. He has co-authored over 90 publications and co-invented more than 50 patents. His work has contributed to the development of at least six clinical candidates, including Ribociclib (Kisqali®), which was recently approved by the FDA as a first-line treatment for HR+/HER2- metastatic breast cancer.

Notable Works

• Fragment-based lead discovery: leads by design
• A novel phase-switching protecting group for multi-step parallel solution phase synthesis
• The Application of Quantitative Analytical Constructs for Chemistry Optimization, Monomer Rehearsal and Reactivity Prediction in Solid Phase Library Synthesis
• Fragment-based Drug Discovery of the Synthetic Small Molecule HSP90 Inhibitor AT13387
• Bicyclic Heterocyclic Compounds as FGFR Inhibitors

- Imidazole Derivatives and their Use as Modulators of Cyclin-Dependent Kinases

Miles Congreve

Chief Scientific Officer at Isomorphic Labs

Miles Congreve is a researcher in the field of biochemistry and drug discovery. He currently serves as Chief Scientific Officer at Isomorphic Labs. Congreve obtained a BSc in biological chemistry from the University of Leicester and a PhD in synthetic chemistry from the University of Cambridge.

Career

Congreve began his career at Glaxo in 1993 before joining Astex Technology (now Astex Therapeutics, part of Otsuka) in 2001. At Astex, he established the chemistry team and worked on developing and validating fragment-based drug discovery approaches for structure-based drug design and lead identification. In 2006, he was promoted to Director of Chemistry. During his time at Astex, Congreve and his team successfully delivered results across a broad range of projects, including at least six clinical candidates. He also co-invented Ribociclib (Kisqali®), which received FDA approval as a first-line treatment for HR+/HER2- metastatic breast cancer.

In 2008, Congreve joined Heptares as Head of Chemistry, where he took on responsibility for the overall Discovery team. He has co-authored over 90 publications and is a co-inventor on more than 50 patent filings. Congreve was recognised for his contributions to GPCR drug discovery with the Malcolm Campbell Memorial Prize in 2015, awarded by the UK Royal Society of Chemistry's Biological and Medicinal Chemistry Sector.

Research Focus

Congreve's research focuses on drug discovery, with an emphasis on fragment-based lead discovery and structure-based drug design. He has co-authored publications on topics such as oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B, analytical techniques for small molecule solid-phase synthesis, and the development of potent inhibitors of thrombin. Congreve has also worked on projects related to Alzheimer's disease, cancer, and diabetes.

Affiliations

• Isomorphic Labs (current)
• Heptares Therapeutics (2008-present)
• Astex Pharmaceuticals/Astex Therapeutics (2001-2008)
• Glaxo (1993-?)
• University of Cambridge (PhD)
• University of Leicester (BSc)