Creating new anti-viral and cancer drugs
ProTide technology is a pro-drug strategy with proven capacity to generate new drug candidates for nucleoside-based antiviral and anti-cancer indications.
Finding new drugs to treat some of the world's most common forms of virus and cancers is a key challenge for scientists and pharmaceutical companies worldwide. The challenge remains to develop antivirals for the treatment of HIV, hepatitis B (HBV) and HCV.
Professor Christpher McGuigan and his team at Cardiff University researched the design of novel chemically-protected phosphate prodrug groups or motifs, which later became known as 'ProTide' technology.
In collaboration with the virology group of Professor Balzarini (Rega Institute of Katholieke Universiteit Leuven, Belgium) the McGuigan team investigated how the targeted attachment of ProTide motifs onto precursor nucleoside drugs enhanced drug entry into target cells and overcame nucleoside drug resistance.
The McGuigan-led research showed the chemically-protected phosphate prodrugs to be stable to common extracellular deactivating enzymes that typically cause poor pharmacokinetics. Importantly the lipophilic character of the ProTide motif enables intracellular prodrug delivery by passive membrane permeation rather than relying on active transport.
This is a highly desirable pharmaceutical feature for delivery of drugs to intracellular targets and for oral drug administration. Crucially the team showed it could manipulate the design of the ProTide to maximise the efficacy of a drug while minimising its potential systemic toxicities.
Investing in future research
Out-licencing of the intellectual property for the technology has enable reinvestment in facilities within the School of Pharmacy to expand the programme of research.
McGuigan's team has been at the forefront of candidate ProTide drug development particularly in anti-virals, including the design of a hepatitis C (HCV) drug candidate. The ProTide technology has also been applied to modify and improve nucleoside-based anticancer agents.
Significant worldwide commercial impact has been delivered from the research. Multinational pharmaceutical companies and smaller drug discovery firms in the USA and Europe have implemented the ProTide technology on candidate and existing therapeutics.
The technology is transforming the prospects of antiviral and anti-cancer nucleoside agents, for example, Nucana. These users have invested in ProTide technology either through direct research partnerships with Cardiff University or by independently adapting the techniques described by the team to their own proprietary agents, eg, Gilead.