Urea motif containing compounds and derivatives thereof as antibacterial drugs - aBACTER
Dr Franziska Mandl, TU Munich – Project aBACTER; Dr Mathias Hackl, TU Munich – Project aBACTER; Dr Christian Fetzer, TU Munich – Project aBACTER; Dr Elena Kunold, Karolinska Institut; Dr Philipp Le, Roche Diagnostics GmbH; Dr Vadim Korotov, Helmholtz Centre for Infection Research; Prof. Stephan Sieber, TU Munich
aBacter - Technical University of Munich
Antimicrobial resistance (AMR) is a growing threat with serious health and economic consequences. Newest data published by the European Centre for Disease Prevention and Control (ECDC) showed again an increase of bacterial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Moreover, the study revealed that these bacteria are responsible for about 25% of infections caused by antimicrobial resistant bacteria and almost 30% of AMR-related deaths. Approved antibiotics rapidly induce resistance in bacteria and only show limited treatment options in case of biofilms and persister cells. To overcome these limitations there is an urgent need for structurally novel antibacterial compounds with new modes of action lacking resistance development.
aBACTER is an innovative pre-seed project focused on the development of novel antibiotics exhibiting excellent potency against multi-resistant bacteria to tackle these challenges. Broad-spectrum activity against Gram-positive WHO-priority pathogens, such as MRSA and VRE, no detectable resistance-development, anti-biofilm and anti-persister activity comprise our unique antibiotic profile. First Proof-of-Concept studies in mice showed significant reduction of the bacterial load in heart and liver. Hence, key indications for market entry comprise endocarditis and liver abscess.
• Oral available systemic antibiotic
• Eradication of established biofilms
• Treatment of endocarditis
• Killing of persistent cells
• Library containing 400 compounds generated
• In vitro characterization of key antibacterial properties
• Pharmacokinetic profiles determined
• In vivo efficacy currently under investigation
Filed in 2016. PCT nationalization in EU, USA, Canada, Singapore, Japan and China. Follow-up application under preparation.
P. Le, E. Kunold, R. Macsics, K. Rox, M. C. Jennings, I. Ugur, M. Reinecke, D. Chaves-Moreno, M. W. Hackl, C. Fetzer, F. A. M. Mandl, J. Lehmann, V. S. Korotkov, S. M. Hacker, B. Kuster, I. Antes, D. H. Pieper, M. Rohde, W. M. Wuest, E. Medina and S. A. Sieber, “Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms”, Nat. Chem., DOI:10.1038/s41557-019-0378-7.