Chlorotonil as a Novel Antibiotic and Antiparasitic Therapeutic
Keywords
Gram-positive antibiotic, malaria, gametocytocidal activity, antimalarial resistance, Plasmodium falciparum
Invention Novelty
Semi-synthetic generation of improved Chlorotonil derivatives with potent activity against multi-drug-resistant Gram-positive bacteria, Plasmodium falciparum, and Mycobacterium tuberculosis.
Value Proposition
Asset in lead optimization stage with a new mode of action.
• Production at scale: Gram quantities are achievable without optimized fermentation, dehalogenation, or synthetic reactions.
• Main target: Complex, non-lytic MoA with nanomolar cellular killing through depolarization of the membrane and secondary enzyme targets involved in peptidoglycan and protein synthesis.
• Indications: Vancomycin-resistant Enterococcus, Methicillin-resistant Staphylococcus aureus, and Malaria.
• Resistance likelihood: No resistance developed at >1x MIC in tested bacteria, nor in P. falciparum.
These features highlight the potential to meet an unmet medical need in WHO critical human pathogens.
In vivo proof of concept of lead asset, dehalogenil, in two disease models (WO2024231481).
Technology Description
• In vitro activity: MIC90 = 0.025 μg/ml (Staphylococcus) and 0.0125 μg/ml (Enterococcus). IC50 = 0.0039 μM (P. falciparum Dd2)
• In vivo PD: Potential for endocarditis therapy, PoC in thigh, sepsis, and foreign-body infection model with S. aureus.
• Safety and tolerability: No treatment-related effects at effective doses in mice, no red flags in Cerep, seahorse profiling, ROS induction, and no signs of cardiotoxicity or hepatotoxicity in zebrafish larvae.
Commercial Opportunity
The technology is available for co-development and in-licensing partnerships.
Development Status
Technical scale-up of optimized production is planned; further PK/PD studies are planned.
Patent Situation
Two international PCT applications have been filed (WO2019092030A1 and WO2024231481). National phases were initiated in 2020 in EP and the US.
Further Reading
Delahogenil synthesis – Hofer et al., 2024. ACIE, 63, 19
MoA article – Deschner et al., 2025. Cell Chemical Biology, 32, 4
Licensing Contact
Dr Alejandro Restrepo Arango
Technology ScoutT: +49 531 618120-92
restrepo@ascenion.de
Institute of Origin
