Cardiff University's ProTide technology enters clinical trials to target drug resistant cancers
Our innovative ProTide technology has been used to develop drug compounds that could make cancer treatments more effective.
Millions of cancer patients are prescribed chemotherapy which uses nucleoside-based drugs to try and target cancer cells. However, some types of cancer are resistant to these drugs. Cardiff University researchers have used their pro-nucleotide (ProTide) technology to develop new compounds which work in conjunction with existing chemotherapy drugs to make them more effective. Three of our anti-cancer ProTides have entered clinical trials, bringing new hope for patients living with some of the hardest to treat cancers.
The limitation of some chemotherapy drugs
Chemotherapy drugs are used to stop the uncontrolled growth of cancer cells. A major class of chemotherapy drugs are called Nucleoside analogues which prevent tumours from growing by inhibiting DNA from replicating which, in turn, leads to the death of cancer cells. However, some cancer cells can resist nucleoside-based drugs making them less effective at treating certain types of cancer. Chemotherapy drugs also target healthy cells as well as cancer cells resulting in patients experiencing severe side-effects.
What is Cardiff University’s ProTide technology?
In the early 1990s, the late Professor Chris McGuigan led a team of researchers at Cardiff University’s School of Pharmacy and Pharmaceutical Sciences to develop a chemical platform on which to design and synthesize chemical compounds for drug development. This platform is known as ProTide technology.
ProTide technology combines an existing class of drugs called nucleotide analogues with a ‘prodrug’ which is a chemical compound that gets converted inside the human body into a pharmacologically active drug. By adding the prodrug, nucleotide analogues can be delivered into target cells to work more effectively.
Using Cardiff University technology to transform anti-cancer drugs
Our ProTide compounds were initially used to enhance the effectiveness of anti-viral drugs to treat a range of life-threatening viruses. In more recent years, the research team at Cardiff University's School of Pharmacy and Pharmaceutical Sciences has expanded the use of ProTides to target drug-resistant cancers.
By the end of 2021, our ProTides were in clinical development across a range of clinical studies including:
Clinical trials for a derivative of 5-fluorouracil designed to target advanced solid tumours
This trial has demonstrated positive benefits in terms of activity and safety compared to the standard 5-fluorouracil treatment of solid cancer tumours. Further clinical studies are now underway to determine how effective this ProTide could be when used in conjunction with different colorectal cancer drugs.
Clinical trials for a ProTide transformation of cordycepin
Cordycepin demonstrated potent anti-cancer activity in pre-clinical studies but had not been developed as chemotherapy drug due to its rapid metabolic breakdown. Our ProTide transformation of Cordycep is currently undergoing a clinical study in patients with solid tumours.
These trials could lead to enhanced treatments to tackle a range of hard-to-treat cancers in the coming years.
In August 2009, a new UK-based biopharmaceutical company called NuCana entered into a research collaboration and license agreement with Cardiff University based on the strength of our ProTide research. NuCana was set up to use our ProTide technology to transform some of the most widely prescribed chemotherapy drugs into more effective and safer medicines for patients.
- Cardiff University developed a chemical platform on which to design and synthesize chemical compounds for drug development. This platform is known as ProTide technology.
- ProTide compounds work in conjunction with existing anti-cancer drugs to make them more effective.
- Three of our ProTides are now in clinical trials bringing hope to patients living with hard-to-treat cancers.
- Slusarczyk, M. et al. 2018. Synthesis and biological evaluation of 6-substituted-5-fluorouridine ProTides. Bioorganic and Medicinal Chemistry 26 (3), pp.551-565. (10.1016/j.bmc.2017.11.037)
- Slusarczyk, M. et al. 2014. Application of ProTide technology to Gemcitabine: A successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development. Journal of Medicinal Chemistry 57 (4), pp.1531-1542. (10.1021/jm401853a)
- McGuigan, C. et al. 2011. Phosphoramidate ProTides of the anticancer agent FUDR successfully deliver the preformed bioactive monophosphate in cells and confer advantage over the parent nucleoside. Journal of Medicinal Chemistry 54 (20), pp.7247-7258. (10.1021/jm200815w)
- Congiatu, C. et al., 2006. Novel potential anticancer naphthyl phosphoramidates of BVdU: Separation of diastereoisomers and assignment of the absolute cConfiguration of the phosphorus center. Journal of Medicinal Chemistry 49 (2), pp.452-455. (10.1021/jm0509896)