Second anti-viral Drug discovered by Prof McGuigan’s group enters human clinical trials
13 May 2010
Cardiff Team at Inhibitex HQ in Georgia (Spring 2010)
l-r Dr Mohamed Aljarah, Karoline Madela, Prof Chris McGuigan
In an exciting breakthrough, another anti-viral drug, first synthesised in Prof Chris McGuigan’s laboratory in the Welsh School of Pharmacy just 18 months ago, is now being tested in humans as part of a phase I clinical trial, through a long-term deal with U.S. company Inhibitex.
The new compound, known by its abbreviation INX-189, is active against the hepatitis C virus, which affects some 170 million individuals worldwide (3% of the human population), for which current treatment is poor.
As shown to the right it is active against the virus at nanomolar levels in laboratory tests, killing 50% of viral particles at 10 nanomolar and obliterating them at just 20 nM.
Inhibitex supported Team in Prof McGuigan's lab
l-r Claire Bourdin (PhD), Sarah Jones (tech), Karoline Madela (PhD), Dr Mohamed Aljarah (post doc)
This marks a new chapter in the successful interaction of Prof McGuigan’s lab with Inhibitex, who currently support four members of the team in Cardiff. This collaboration was recognised by Cardiff University by the award of the Innovation Prize in 2008 .
INX-189 is the first Cardiff example of the ‘Pro-Tide’ concept to be tested in humans. This concept was proposed by Chris McGuigan early in his career in Cardiff, whereby a nucleoside drug molecule active against specific viruses or cancer types, can be enhanced through phosphorylation, with subsequent masking of the phosphate group to ensure penetration through the cell wall.
(For a recent scientific paper describing this concept see The Application of Phosphoramidate Protide Technology to Acyclovir Confers Anti-HIV Inhibition by
Marco Derudas, Davide Carta, Andrea Brancale, Christophe Vanpouille, Andrea Lisco, Leonid Margolis, Jan Balzarini and Christopher McGuigan
A current Powerpoint presentation from Prof McGuigan describing Pro Tides is available here. )
potency of INX-189 against HCV compared to two competitor molecules
Potency = 1/EC50 in micromolar
By coincidence, two other Pro-Tides active against hepatitis C are currently in phase I trials, having been developed by other companies, but INX-189 is by far the most potent. The current tests will establish its safety in humans, prior to further testing on efficacy.
Phase I clinical trials with INX-189 have recently been initiated in America by the US-based biopharmaceutical company, Inhibitex Inc., who are well into Phase II clinical trials with the anti-shingles drug FV-100, also synthesised by Prof McGuigan's group.
See also
..
Prof Chris McGuigan
