New Drugs for Brain Tumours: Defining the Physicochemical Parameters for Optimal Imidazotetrazine (Temozolomide) Derivative Prodrug Activation Kinetics

The imidazotetrazine ring system that forms the core of the anticancer drug temozolomide is a fascinating prodrug delivery device. The bicyclic structure bears only three substituents. These fulfil interconnected functions that control solubility, stability, uptake, distribution, prodrug activation and drug release kinetics and finally pharmacology. Surprisingly, only disjointed contributions to rationalising the various substituent contributions have been made.

This project will pursue an integrated programme of analogue synthesis, kinetic studies and in vitro screening against cultured glioma cells and models, to refine understanding of the various substituent effects. The successful outcome will establish tailored and predictable physicochemical parameters to inform future compound design. The ultimate aim is to identify an optimised next-generation temozolomide for advanced pre-clinical development.

Specific Aims

1. Analogue synthesis of a rationally-designed panel of imidazotetrazine and cognate triazene derivatives.
2. Measurement of prodrug activation kinetics and correlation with substituent electronic and steric contributions.
3. In vitro screening of novel agents in 2D and 3D brain tumour cell culture models.

The student will join a successful, motivated multidisciplinary team with expertise in medicinal chemistry and preclinical toxicology and pharmacology with the aim of identifying an agent to progress towards advanced preclinical testing and ultimately the clinic. They will work in the University of Bradford Institute of Cancer Therapeutics.

Admissions Requirements

At least 2:1 honours degree in Chemistry, Medicinal Chemistry, Pharmacy or related subjects. An MSc in any of these areas is an advantage.

How to apply

Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account and select 'Full-time PhD in Pharmacy' as the course, and then specify the project title when prompted.

About the University of Bradford

Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities.

Faculty of Life Sciences

The faculty comprises a mixture of academic divisions, research centres and outreach facilities. We provide high-quality teaching with a professional focus and engage in cutting-edge research – which we seek to apply through our extensive links with industry and business. We also offer a wide range of postgraduate taught and research courses.

Many of our academics are active researchers and international research experts.

Our interdisciplinary research themes are focus on:

• Computational and Data-driven Science
• Interface of Chemistry Biology and Materials
• Health, Society, People and Place
• The Life Course

Our research centres include:

• Centre for Pharmaceutical Engineering Science
• Digital Health Enterprise Zone
• Institute of Cancer Therapeutics
• Wolfson Centre for Applied Research

University investment in research support services, equipment and infrastructure provides an excellent research environment and broad portfolio of developmental opportunities. 

Positive Action Statement

At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students.

Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level. 

These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies.