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RISE gives small enterprises good advice in ADME studies

Antibiotic-resistant bacteria are a growing problem that puts certain drugs at risk of becoming ineffective. The Swedish company QureTech Bio's vision is to develop drugs to combat infectious diseases and the presence of antibiotic resistance. 

QureTech Bio has developed new substances that can either act as traditional antibiotics, enhance the effect of existing antibiotics or disarm bacteria instead of killing them. 

– The expert competence and resources that RISE has contributed have been invaluable for the continued development of our projects. It has given us the guidance we need to be able to take the next step to refine our substances and take them closer to a new treatment alternative for infectious diseases, says Annica Rönnbäck, project coordinator at QureTech Bio. 

In one of QureTech's projects, RISE has contributed expertise in ADME and toxicology to evaluate and analyse results from an animal study, but also with advice and guidance for alternatives going forward for further optimization of the substance class. 

– Being open and clear in communication and showing ways to get around obstacles that arise along the way is a very important part of our way of working with our customers, says Ian Cotgreave, Vice President at the department of Chemical and Pharmaceutical Safety at RISE. That new molecules and substances do not always behave the same in animal studies as when tested in test tubes is a natural part of the development process, but that is of course not what you as a developer want to discover when you have a main candidate that you hope for. Then it may sometimes be necessary to go back one step and look at more similar molecular structures to find a new candidate. 

In order to interpret and understand results from efficacy studies and toxicological in vitro and in vivo studies in early drug projects, it is important to have knowledge of the ADME properties of the substances, that is how they are absorbed, distributed, metabolised and excreted in the body. A substance that has a good effect in vitro can prove to be completely ineffective in the body due to poor ADME properties. To develop drugs, it is therefore important to find a balance between efficacy and ADME properties, while there must be a safety margin in relation to toxicity.  

– By using prediction models, it is possible to predict certain properties based on the chemical structure even before the first experiments are performed, explains Anna-Karin Sternbeck, expert in ADME at RISE. The prediction models enable a large number of project substances to be analysed simultaneously. The most promising substances are then selected for testing in ADME experiments. As new ADME and effect results are added, these can be integrated into different calculation models to determine whether there is potential for the substances to give the desired effect at the desired dose in humans. It often turns out that the substances with the best in vitro effect are not the substances that are most suitable to push further in the project. Ultimately, it is efficacy, ADME properties and toxicology that together determine which substance has the best potential to become a drug. 

Matilda Bäckberg

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Matilda Bäckberg

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