Project description
Antibiotic development to combat multidrug-resistant infections
The threat of antimicrobial resistance (AMR) is one of the most pressing global health challenges today, with multidrug-resistant (MDR) pathogens rapidly spreading. The need for new antibiotics is urgent to tackle infections that are no longer treatable by conventional drugs. Current treatments are becoming ineffective, leading to increased mortality and complications. The search for innovative antibiotic targets is crucial in overcoming this crisis. In this context, the ERC-funded AnLeadOp project aims to optimise a promising new class of antibiotics targeting the bacterial sliding clamp (DnaN), a breakthrough identified in previous research. By evaluating their antibacterial properties, and assessing their in vivo effectiveness, the project seeks to develop preclinical lead candidates to combat MDR bacterial infections.
Objective
The bacterial sliding clamp (DnaN) is an innovative target for the development of novel antibiotics, which are urgently needed to overcome the alarming antimicrobial resistance crisis. In the previous ERC starting grant (NovAnI), we discovered a novel DnaN inhibitor (WAM-N17) with promising broad-spectrum antibacterial activity including multidrug-resistant (MDR) pathogens. In this PoC project, we will optimize the antibacterial potency and spectrum and characterize the in vivo pharmacokinetic (PK) and pharmacodynamic (PD) properties of the WAM-N17 class so as to develop preclinical lead candidates for the treatment of bacterial infections, especially those caused by MDR germs. To achieve this goal, we will pursue three main activities. (i) Design and synthesis of 25–30 compounds (in two rounds) with modifications focusing on improving the anti-Gram-negative activity as well as target identification through chemical probes to further validate DnaN and identify other potential targets in bacteria. (ii) Evaluation of antibacterial activity, target binding/inhibition, and in vitro ADME-T (absorption, distribution, metabolism, excretion, toxicity) characterization for all new compounds. The frontrunners will be profiled for antibacterial activity against an extended panel of Gram-negative and MDR clinical isolates and subjected to mode of action (MoA) and target-identification studies. The most promising ten compounds will be submitted for in vivo PK studies and the best two lead candidates will be tested in a proof-of-concept in vivo efficacy study using relevant infection mouse models. (iii) Ultimately, we will file a patent to secure our intellectual property rights and continue to move this class of compounds forward into preclinical and then clinical studies in collaboration with a pharmaceutical industry partner. The knowledge that will be gained from this PoC project is essential to develop an urgently needed new antibiotic with an unprecedented mode of action.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance multidrug resistance
You need to log in or register to use this function
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-POC2
See all projects funded under this callHost institution
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
38124 Braunschweig
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.