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Design, Synthesis and Biological Evaluation of novel inhibitors of the JAK-STAT signalling pathway with potential application as immune oncology agents

Project Description

Small molecule inhibitors of the JAK-STAT signalling pathway often possess interesting biological properties with many displaying potent anti-proliferative activity towards cancer cell lines. An example of such an inhibitor is clinical candidate WP1066. Recently, a successful collaborative project between the members of the supervisory team, uncovered new analogues of WP1066 with high biological potency. The goal of this project will be to develop and optimise chemo-enzymatic approaches to novel, specifically designed analogues belonging to this structural class and to carry out detailed assessment of their biological properties. The synthetic approach to the target molecules will involve application of amine oxidase and/or transaminase enzymes for the preparation of key chiral synthetic intermediates. Biological assessment will include measurement of anti-proliferative activities using MTT and SRB assays as well as evaluation of the affects the compounds have on the inflammatory response.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or the overseas equivalent) in Biological and/or Medicinal Chemistry or a related area. Candidates with experience in contemporary organic synthesis and with an interest in biocatalysis and/or oncology are encouraged to apply.

Contact for further Information:
Dr Roger Whitehead

Funding Notes

Applications are invited from self-funded students.
For UK/EU tuition fees are £15,500 and International are £30,500 for 2019/20 academic year.

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