University of Oxford Featured PhD Programmes
University of Oxford Featured PhD Programmes
University of Oxford Featured PhD Programmes

Development of heterocyclic pharmacophores using diversity-oriented synthesis

Faculty of Life Sciences

About the Project

Diversity-oriented synthesis (DOS) is a modern chemical tool, which aims to synthesise small molecules that cover new chemical space with the possibility of finding unexplored biological targets or pathways that may be important for disease progression. The development of novel chemical entities (NCEs) is very important to the field of chemical genetics where chemical probes are used to probe known or unknown biological targets.

This project will use DOS to enable the preparation of libraries of NCEs comprising heterocyclic pharmacophores, which will be used to probe the functional activity of unexplored targets. DOS will also be used to discover novel tool compounds to probe regulation and functional activity of (i) aldehyde dehydrogenase (ALDH) isoforms highly expressed in cancer stem cells, (ii) cytochrome P450 (CYP) isoforms expressed in solid tumours or (iii) aldo-keto reductase 1C3 (AKR1C3). Conventional approaches such as computational modelling and medicinal chemistry will be employed in parallel to the use of DOS in order to develop chemical probes for enzyme interrogation. Effective chemical tool compounds will be modulated with the aim to develop fluorophores with commercial potential and/or tumour selective therapeutics with clinical potential to treat cancer patients.

Funding Notes

This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee may also apply to this project, in addition to the tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support.

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