Dr Ian Hardcastle received his first degree from Bristol University in 1987. He received his PhD in organic synthesis in 1990, from Manchester University, with Dr Peter Quayle. This was followed by a post-doctoral fellowship in the CRC Centre for Cancer Therapeutics at The Institute of Cancer Research with Professor Mike Jarman. Work at the ICR included: studies of the structure activity relationships for tamoxifen analogues, studies into the genotoxic mechanism of tamoxifen. The development of the novel CYP17a inhibitor abiraterone (Zytiga) licenced for the treatment of castrate resistant prostate cancer. The synthesis of novel inhibitors of the Farnesyl Transferase enzyme and the development of novel template-based combinatorial libraries for lead discovery.
In November 1999 he joined the Drug Discovery Programme in the Cancer Research Unit now the Newcastle Cancer Centre at the Northern Institute for Cancer Research (NICR), Newcastle University, as a Lecturer in Medicinal Chemistry and is now Reader in Medicinal Chemistry.
Principal Research Interests: medicinal chemistry and drug discovery, targetted anti-cancer agents.
The medicinal chemistry team (C Cano, BT Golding, RJ Griffin, IR Hardcastle) is part of the Drug Discovery and Imaging Team within the NICR. Working closely with basic cancer biologists, structural biologists, pharmacologists, imaging specialists, and clinical scientists, the overall aim of the programme is to discover novel small-molecule inhibitors of cancer targets which can be developed into new treatments for cancer patients.
Targets are selected based on an understanding of the underlying cancer biology and their clinical relevance. Current projects include the discovery of small-molecule MDM2-p53 and MDMX-p53 protein protein interactions, the discovery of small-molecule ERK5 inhibitors, the discovery of small-molecule Nek2 inhibitors, and chemical biology studies for other novel cancer targets.
Contemporary, medicinal chemistry methods are used in all projects. including high throughput screening to identify hit compounds (through external collaborations), and structural biology to enable rational drug-design. High-throughput synthesis, utilising solution-and solid-phase multiple-parallel approaches and microwave heating, is used to determine structure-activity relationships and rapidly optimise biological activities and pharmaceutical properties for lead compounds.Computational chemistry and informatics are essential tools, and the group uses the Dotmatics database suite, and Optibrium's StarDrop for predicting properties.
School of Chemistry
BSc/MChem Chemistry and Chemistry with Medicinal Chemistry
CHY1102 - Fundamentals of Biological and Medicinal Chemistry
CHY2401 - Structural Chemistry
CHY8421/8821 - Advanced Methods in Drug Discovery
CHY8411/8412 - Research Project
MSc Drug Chemistry
CHY8821 - Modern Methods in Drug Discovery
CHY8810 - Research Preparation
CHY8811 - Research Project
CHY8827 - Biological and Medicinal Chemistry
MRes Translational Medicine and Therapeutics - L12 The role of medicinal chemistry