Antibiotics

Abstract

Mass production and the development of new miracle antibiotics are being overshadowed by reports that we are running out of antibiotics and have reached a point where there are very few in the pipeline and potentially no treatment alternatives left for some bacterial infections – some caused by foodborne bacteria. One of its findings was that one-third of antibiotic prescriptions are not needed, but are written to humor the patient In the heady early days of antibiotic use, resistant infections did occur, but a steady flow of new antibiotics provided alternative treatments. According to the WHO, this is the state of the antibiotic pipeline as of 2025: A total of 90 products were identified in clinical development – 50 traditional antibacterial agents and 40 non-traditional agents. With a likely success rate of 10 percent to 20 percent from phase I trials to approval, only a few of the substances can be expected to reach the market within 10 years.

Abstract

Understanding compound selectivity is vital when designing novel pharmaceuticals. The extent of on- and off-target effects, or potential polypharmacology, informs modifications to develop safe and effective drugs. In this white paper we present a data-driven drug design method which visualizes binding site comparisons across a protein family, to deeply understand selectivity and pocket druggability. These Ensemble Hotspot Maps" are derived from peer-reviewed, experimentally-generated data in the Cambridge Structural Database, and automated to rapidly and visually guide target validation and drug design."

Abstract

Moreover, we propose the use of clinical outcome pathways (COPs), originally introduced as a framework linking mechanistic biology to clinical outcomes, as a basis for guiding the use of NAMs in biomedical research and for supporting a more systematic implementation of non-animal approaches. To broaden the adoption of NAMs, it is essential to move beyond the question of regulatory obligation, 'do I have to use animal models?', and instead focus on the scientific possibilities: 'how can NAMs enhance and transform my research?'. More specifically, COPs could help to: define which biological events are most critical to capture in relation to disease onset, progression or therapeutic response, assess whether currently available NAMs represent these events with sufficient biological relevance, identify where multiple NAMs need to be combined to capture interacting processes across cell types, tissues, organs or disease stages, highlight areas where no suitable NAM currently exists, thereby guiding the prioritization of future model development, support the design of testing strategies in which NAMs are selected based on their ability to address clearly defined mechanistic questions rather than on convenience alone, facilitate interpretation of NAM-derived findings by anchoring individual readouts within a broader disease pathway, thereby clarifying what a given result may mean in relation to downstream clinical outcomes, and improve the translational value of NAM-based research by more explicitly linking non-animal experimental outputs to clinically meaningful endpoints. Authors and Affiliations Finnish Hub for Development and Validation of Integrated Approaches, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland Tampere Institute for Advanced Study, Tampere University, Tampere, Finland Institute of Medical Biochemistry, Medical University Innsbruck, Innsbruck, Austria Department of Information Engineering, University of Pisa, Centro 3R, Pisa, Italy 3Rs Centre Utrecht, Utrecht University, Utrecht, the Netherlands i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal Nuno H. Franco & I. Anna S. Olsson Austrian Institute of Technology, Vienna, Austria Faculty of Medicine and Dentistry, Danube Private University, Krems, Austria Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway Contributions Beyond the first author, the author list is in alphabetical order.