Description of impactA first-in-class anticancer agent discovered in Thurston’s laboratory at the University of Portsmouth in the 1990s has been commercially developed and clinically evaluated over the last two decades. A spin-out company, Spirogen Ltd, was established in 2000 to commercialise the intellectual property generated from the underpinning research, the company has subsequently been sold to AstraZeneca for $200m.
The drug development group at the University of Portsmouth was headed by David Thurston (Professor of Medicinal Chemistry: 1987-1999) who, during this time, developed close collaborations with colleagues working in the area of DNA structure and protein-DNA interactions (principally Geoff Kneale, Professor of Biomolecular Science & Matt Guille, Professor of Developmental Genetics). Thurston and co-workers initiated a program of medicinal chemistry to synthesise and evaluate analogues with novel or improved DNA-recognition properties.This lead to the design of a new compound, SJG-136, which was successful in Phase I clinical trials where significant patient benefit in the form of partial responses and stabilisation of disease was observed in ovarian and bowel cancer, melanoma and leukaemia. SJG-136 entered Phase II clinical trials in ovarian cancer through the US National Cancer Institute in early 2011, and a further Spirogen-sponsored Phase II clinical trial in leukaemia with two centres in the USA started recruiting in 2013. Related molecules based on this parent compound are in drug programmes being undertaken by Seattle Genetics Inc. and Genentech Inc., leading to additional clinical trials.
There are four major impacts arising from this research:
(a) A highly successful and profitable spin-out company has been created and sustained;
(b) A new technology process has been adopted by the company’s commercial partners;
(c) A new intervention has been trialled with patients;
(d) Clinical outcomes for patient groups have been improved.
|Category of impact||Health & Welfare Impacts, Economic & Commercial Impacts|
|Impact level||Benefit (delivered impact)|
- Anticancer agent
Documents & Links
Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8‘ ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers
Research output: Contribution to journal › Article › peer-review