31st January 2017
InhibOx has been successful in winning nearly £1m of grant funding to continue research into novel antibiotics. The project started four years ago as part of an EU-funded collaboration into multi-drug resistance. Capitalising on drug design, chemical synthesis and biology skills across the consortium, they have discovered new molecules with activity against a range of Gram-negative bacteria. The new money comes from Innovate UK, the UK's innovation agency and will be used design improvements in the activity and anti-resistance properties of the molecules.
The compounds discovered so far have activity against a range of Gram-negative bacteria but need to be improved in terms of level of activity and stability. This class of bacteria (which includes species such as E. coli and Klebsiella) has an extra layer to their cell wall. This provides them with an additional barrier to drug penetration, making them much harder to treat. The new compounds inhibit members of an enzyme class called tRNA synthetases which play a key role in protein biosynthesis.
The next steps are to optimise the molecules to enhance these activity and stability and to monitor the emergence of resistance, which so far, has been very low. The design work will be carried by over the next two years with the aim of developing a candidate ready for clinical testing.
16 January 2017
Promising early results in our antibacterial drug discovery programme suggest we are close to a breakthrough on a new class of antibiotics.
Our antibacterial drug discovery programme focuses exclusively on novel mechanisms of action. Drugs using these novel mechanisms are expected to produce drugs effective against bacteria resistant to existing drug classes.
The news comes shortly after the recent death of a woman who died from a bacterial infection and was reportedly resistant to all available antimicrobial drugs. At present, 700,000 people a year are dying of antibiotic resistance, with the figure expected to rise to 10,000,000 by the year 2050.
Bacterial resistance mechanisms, such as the New Delhi Metallo-beta-lactamase (NDM) present in the reported bacterial infection, can easily spread through a population and tend to confer resistance to multiple drugs of the same class. Consequently, while new variants on existing drugs are useful, they can suffer from rapid emergence of resistance. InhibOx’s patented lead compound, however, is effective against bacteria containing the NDM resistance mechanism, and could prove incredibly valuable in the global fight against antibiotic resistance.
30 November 2016
Prof. Paul Finn has contributed a chapter on Belinostat to the latest volume of "Successful Drug Discovery". Belinostat was approved by the FDA for the treatment of peripheral T-cell lymphoma in 2014. As in the previous volume of this series, the inventors and primary developers tell the stories of 11 recently-introduced drugs that have not previously been covered in textbooks or general references.
As both the co-inventor of Belinostat and leader of the histone deacetylase inhibitor programme through discovery and pre-clinical development, Paul has unique insights into what makes this drug successful.
23 May 2016
Dr. Michael Charlton and Dr. Grace Edmund recently reported our efforts to understand the physical properties and chemical features required to achieve antibacterial activity at the MOE user-group meeting and conference hosted by CCG in Vienna.
Our presentation showcased work from our recent publication on the physiochemical properties of antibacterial compounds and extended it to show how our proprietary ElectroShape virtual-screening technology can be applied to separate antibacterials from biochemical actives. This was coupled with machine-learning techniques that were able to identify multiple areas of chemical space that are significantly enriched in antibacterials.
We also presented a poster outlining our work on the TolC bacterial efflux pump that is responsible for the removal of many potential antibacterials from within the cell before they have time to act. Our analysis of TolC data from the ChEMBL database shows that compounds with intermediate size and polarity are particularly prone to efflux.
19 May 2016
InhibOx welcomes the report "Tackling Drug-Resistant Infections Globally" chaired by Jim O'Neill. The report states that "AMR has increasingly become a problem in recent times because overuse of antimicrobials has increased the rate at which resistance is developing and spreading, but we lack new drugs to challenge these new superbugs. This results in us facing a growing enemy with a largely depleted armoury". It challenges the pharmaceutical industry to work on solutions to the problem.
InhibOx is addressing this challenge through applying its proprietary computational drug design platform to a number of antibacterial projects. These have successfully identified new compound series with antibiotic activity through novel mechanisms of action. We are especially excited about the ability of lead molecules to inhibit harder-to-treat Gram-negative species such as E. coli and ESKAPE pathogens. These series offer great potential for the development of new treatments to combat the growing threat of multi-drug resistant bacterial infections.
1 June 2016
InhibOx and its partners have completed the three-year NABARSI project to target drug-resistant bacteria. InhibOx was awarded funding of €1 million by the European Commission’s 7th Framework Programme as part of a €4.1 million consortium project for the preclinical development of novel treatments for multi-drug resistant bacterial infections. Along with Erasmus MC, (The Netherlands), Latvian Institute of Organic Synthesis (Latvia), University of Leeds (UK) and Omnia Molecular (Spain), InhibOx has discovered exciting antibacterial compounds with a novel mode of action against a range of Gram-negative organisms. The compounds target Leucyl tRNA synthetase, an enzyme involved in protein biosynthesis.
21 April 2016
Prof. W. Graham Richards has written a new book entitled “Entrepreneurship - A case study from two view points” in collaboration with his Oxford Molecular co-founder, Tony Marchington. Published by Wet Zebra, this book charts their journey that saw academic discovery become a then-unique business, floated on the stockmarket.