Stuart Conway's Research at UCLA: A Focus on Medicinal Chemistry and Chemical Biology
Stuart Conway, Ph.D., is a distinguished medicinal chemist and chemical biologist whose research lies at the intersection of chemistry, biology, and medicine. Currently holding the Jung Chair in Medicinal Chemistry and Drug Discovery at UCLA, Conway's work focuses on developing molecular tools to study biological systems, particularly in the fields of epigenetics, hypoxia, and targeted protein degradation. His arrival at UCLA marks a significant addition to the university's chemistry and biochemistry departments, the Jonsson Comprehensive Cancer Center, and the California NanoSystems Institute (CNSI).
Background and Education
Conway's academic journey began with undergraduate studies in Chemistry with Medicinal Chemistry at the University of Warwick from 1994 to 1997, where he conducted research with Professor Andrew Clark. He then pursued his Ph.D. at the University of Bristol from 1997 to 2001, working with Professors Jeff Watkins FRS and David Jane. His independent academic career started in 2003 as a lecturer in Bioorganic Chemistry at the University of St Andrews. He later joined the University of Oxford in 2008 as an Associate Professor and was promoted to Full Professor in 2014.
Contributions to Bromodomain Inhibitor Development
Conway's research has significantly contributed to the development of therapeutically relevant bromodomain inhibitors. These inhibitors represent a promising class of novel anti-cancer drugs that function by interfering in epigenetic processes. Epigenetics focuses on the dynamic network of chemical compounds surrounding DNA, influencing gene expression without altering the underlying DNA sequence. Modern DNA sequencing technology allows scientists to measure epigenetic marks across an entire genome. The compounds he developed underpin therapeutic candidates that have been tested in clinical trials for cancer.
Hypoxia-Activated Pro-Drugs
In collaboration with Ester Hammond, Ph.D., of Oxford University, Conway has worked on developing pro-drugs that are selectively activated in hypoxia, a condition characterized by lower than normal levels of oxygen. Hypoxia is a hallmark of solid tumors. Pro-drugs are chemically modified, inactive drugs that are converted into active drugs in the body after administration. This pro-drug approach offers the potential to improve the therapeutic window, enhance disease-targeting, and increase safety for various drug modalities.
Chemical Probes for Protein Proximity
Conway's recent work centers around developing chemical probes that function by inducing proximity between two proteins to alter their function. This innovative approach allows for the manipulation of protein interactions, offering new avenues for therapeutic intervention.
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Key Publications
Conway's research is documented in numerous peer-reviewed publications, including:
- Two Color Imaging of Different Hypoxia Levels in Cancer Cells: Published in the Journal of the American Chemical Society, this work focuses on imaging hypoxia levels in cancer cells. (L. D. Wallabregue, H. Bolland, S. Faulkner, E. M. Hammond, S. J. Conway. J. Am. Chem.)
- Identification of Histone Peptide Binding Specificity and Small-Molecule Ligands for the TRIM33α and TRIM33β Bromodomains: This study, published in ACS Chemical Biology, identifies histone peptide binding specificity and small-molecule ligands for TRIM33α and TRIM33β bromodomains. (R. Sekirnik, J. K. Reynolds, L. See, J. P. Bluck, A. R. Scorah, C. Tallant, B. Lee, K. B. Leszczynska, R. L. Grimley, R. I. Storer, M. Malattia, S. Crespillo, S. Caria, S. Duclos, E. M. Hammond, S. Knapp, G. M. Morris, F. Duarte, P. C. Biggin, S. J. Conway. ACS Chem.)
- Controlling Intramolecular Interactions to Develop Selective, High-Affinity Ligands for the CREBBP Bromodomain: This research, featured in the Journal of Medicinal Chemistry, details the development of selective, high-affinity ligands for the CREBBP bromodomain by controlling intramolecular interactions. (M. Brand, J. Clayton, M. Moroglu, M. Schiedel, S. Picaud, J. P. Bluck, A. Skwarska, A. K. N. Chan, C. M. C. Laurin, A. R. Scorah, K. F. L. See, T. P. C. Rooney, O. Fedorov, G. Perell, W. A. Cortopassi, K. E. Christensen, R. I. Cooper, R. S. Paton, W. C. K. Pomerantz, P. C. Biggin, E. M. Hammond, P. Filippakopoulos, S. J. Conway. J. Med.)
- Development and pre-clinical testing of a novel hypoxia-activated pan KDAC inhibitor: Published in Cell Chemical Biology, this paper discusses the development and pre-clinical testing of a novel hypoxia-activated KDAC inhibitor. (Skwarska, E. D. D. Calder, I. N. Mistry, D. Sneddon, S. J. Conway, E. M. Hammond.)
- Stereo- and regio-defined DNA-encoded chemical libraries enable efficient ligand discovery for conditional CAR-T cell activation and for tumor targeting: This work explores the use of DNA-encoded chemical libraries for ligand discovery in CAR-T cell activation and tumor targeting. (N. Favalli, G. Bassi, C. Pellegrino, J. Millul, R. De Luca, S. Cazzamalli, S. Yang, A. Trenner, N. Mozzafari, R. Myburgh, M.Moroglu, S. J. Conway, A. Sartori, M. M. Manz, R. A. Lerner, P. Vogt, J. Scheuermann, D. Neri.)
- Optimization of 3,5-Dimethylisoxazole Derivatives as Potent Bromodomain Ligands: This article, published in the Journal of Medicinal Chemistry, details the optimization of bromodomain ligands. (Hewings, David S.; Fedorov, Oleg; Filippakopoulos, Panagis; Martin, Sarah; Picaud, Sarah; Tumber, Anthony; Wells, Christopher; Olcina, Monica M.; Freeman, Katherine; Gill, Andrew; Ritchie, Alison J.; Sheppard, David W.; Russell, Angela J.; Hammond, Ester M.; Knapp, Stefan)
- A Series of Potent CREBBP Bromodomain Ligands Reveals an Induced-Fit Pocket Stabilized by a Cation-π Interaction: This study, featured in Angewandte Chemie International Edition, reveals an induced-fit pocket stabilized by a cation-π interaction in CREBBP bromodomain ligands. (Rooney, Timothy P. C.; Filippakopoulos, Panagis; Fedorov, Oleg; Picaud, Sarah; Cortopassi, Wilian A.; Hay, Duncan A.; Martin, Sarah; Tumber, Anthony; Rogers, Catherine M.; Philpott, Martin; Wang, Minghua; Thompson, Amber L.; Heightman, Tom D.; Pryde, David C.; Cook, Andrew)
- Development and pre-clinical testing of a novel hypoxia-activated KDAC inhibitor: This article, published in Cell Chemical Biology, discusses the development and testing of a hypoxia-activated KDAC inhibitor. (Skwarska, Anna; Calder, Ewen D. D.; Sneddon, Deborah; Bolland, Hannah; Odyniec, Maria L.; Mistry, Ishna N.; Martin, Jennifer; Folkes, Lisa K.; Conway, Stuart J.; Hammond, Ester M.)
Affiliations and Recognition
Conway is affiliated with several prominent institutions within UCLA, including the Department of Chemistry and Biochemistry, the Jonsson Comprehensive Cancer Center, and the California NanoSystems Institute (CNSI). These affiliations underscore the interdisciplinary nature of his research and its relevance to both fundamental science and translational medicine.
Conway is a Fellow of the Royal Society of Chemistry (FRSC). He has received several awards, including The EFMC Prizes for Young Medicinal Chemists, The UCB-Ehrlich Award for Excellence in Medicinal Chemistry, and The Robert M. Scarborough Award. In April 2024, UCLA cancer researchers, including Conway, received the Team Science Award from the Melanoma Research Alliance. He also served as the President of the RSC Organic Division.
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