Sustaining Innovation Alumni

Dr Honorine Lebraud

Chemistry, Astex Pharmaceuticals

This project explored the potential of the Inverse Electron Demand Diels Alder (IEDDA) cycloaddition (click chemistry) to support drug discovery projects.

We investigated the use of the IEDDA for the determination of the selectivity profile and target engagement of lead compounds, for the cellular localisation of proteins via fluorescence imaging and also for the induction of protein degradation.

Honorine Lebraud is currently Alliance Management Associate, Astex Pharmaceuticals, UK.

Recent publications:

Lebraud et al., Highly Potent Clickable Probe for Cellular Imaging of MDM2 and Assessing Dynamic Responses to MDM2-p53 Inhibition. Bioconjugate Chem. 2018; 10.1021/acs.bioconjchem.8b00315

Lebraud., et al., Quantitation of ERK1/2 inhibitor cellular target occupancies with a reversible slow off-rate probe. Chem. Sci. October 2018, Issue 37;

Lebraud, H. and Heightman, T. D. Protein degradation: a validated therapeutic strategy with exciting prospects. Essays in Biochemistry. 2017 Nov8;61(5):517-527. Doi: 10.1042/EBC20170030

Sipthorp, J.; Lebraud, H.; Gilley, R.; Kidger, A. M.; Okkenhaug, H.; Saba-El-Leil, M.; Meloche, S.; Caunt, C. J.; Cook, S.; Heightman, T. D. Visualization of Endogenous ERK1/2 in Cells with a Bioorthogonal Covalent Probe. Bioconjugate Chemistry (2017) DOI 10.1021/acs.bioconjchem.7b00152.

Lebraud, H.; Wright, D. J.; Johnson, C. N.; Heightman, T. D. Protein degradation by in-cell self-assembly of PROTACs. ACS Central Science, 2016; DOI 10.1021/acscentsci.6b00280

Lebraud, H.; Wright, D. J.; East, C. E.; Holding, F. P.; O’Reilly, M.; Heightman, T. D. In-gel activity-based protein profiling of a clickable covalent ERK1/2 inhibitor. Molecular BioSystems, 2016; 10.1039/c6mb00367b.

2017 Chemical Biology Poster Prize – Poster prize sponsored by RSC and won at the Chemical Biology Symposium, London.

2016 Vocation for Medicinal Chemistry – Poster prize sponsored by the Laboratoires Servier and won at the 52nd International Conference on Medicinal Chemistry, Caen.