School of Cardiovascular & Metabolic Health

Dr. Blair’s research focuses on the discovery and development of targeted therapeutics against a broad-spectrum of disease indications, designed to exploit disease-associated protein complexes with unparalleled precision; treating the disease whilst minimising the risk of side-effects. Having recently received industry sponsorship from Bristol Myers Squibb and Evotec, Dr. Blair will be utilising the expertise of both industry partners to accelerate the development of a first-in-class MDM2 dimerisation Disruptor (DRx-992). MDM2, and its close homologue MDMX, are major drivers of several haematological and solid cancers. Existing MDM2-targeted therapies provide eligible patients with short-lived treatment response, largely due to their inability to suppress MDM2 (and MDMX) beyond their p53-dependent roles and therefore offering no therapeutic benefit to patients harbouring a TP53 gene mutation (gene that encodes p53). Through disrupting MDM2 dimerisation (essential for its E3-ligase activity), DRx-992 targets MDM2 in both a p53-dependent and p53-independent context – broadening the therapeutic window beyond TP53 wild-type cancers to TP53 mutant, and offering a potential therapeutic approach to neutralising MDM2 whilst concomitantly reducing the risk of treatment resistance. Successful completion of this Lead Optimisation project will enable subsequent pre-clinical evaluation, where Dr. Blair is initially focused on determining the therapeutic potential against two oncology indications with high-unmet needs: (i) relapse/refractory acute myeloid leukaemia and (ii) high-risk neuroblastoma. Supporting this research is Prof. George Baillie, Prof. Helen Wheadon, Dr. Gillian Horne and Prof. Deborah Tweddle.

First published: 20 February 2025