Murepavadin
InvestigationalAlso known as: POL7080, RG7929
A first-in-class cyclic antimicrobial peptide targeting the LptD outer membrane protein of Pseudomonas aeruginosa. The first OMPTA (outer membrane protein targeting antibiotic) to reach clinical development. IV formulation discontinued due to nephrotoxicity; inhaled formulation continues Phase 3 development for cystic fibrosis and bronchiectasis patients.
Research Statistics
Phase 3 antibiotic peptide with multinational clinical experience; LptD outer membrane targeting mechanism is novel and well-characterized, though Phase 3 trials were halted for renal safety.
Research Dossier
Overview
What is Murepavadin and what does the research say?
Mechanism of Action
Murepavadin is the first-in-class Outer Membrane Protein Targeting Antibiotic (OMPTA), specifically targeting the LptD protein in Pseudomonas aeruginosa. Its mechanism is supported by extensive structural and biochemical studies including cryo-EM confirmation of its binding site.
How It Works (Simplified)
Murepavadin acts as a precision weapon against P. aeruginosa by blocking a critical transport system:
Binds to the N-terminal plug domain of LptD, the outer membrane protein that inserts lipopolysaccharide (LPS) into the bacterial membrane.
Locks LptD in a non-functional conformation, preventing new LPS from being inserted into the outer membrane.
Without new LPS, the bacterial outer membrane loses integrity and becomes asymmetric, leading to cell death.
Only P. aeruginosa LptD has the specific structure murepavadin targets, preserving other bacteria and having no effect on human cells.
Scientific Pathways
Lpt Transport Pathway (LPS Assembly)
LPS synthesis (inner membrane) → LptBFGC (ABC transporter)
↓
LptA (periplasm)
↓
Murepavadin ⟶ LptDE (blocked) ⟶ X No LPS insertion
↓
Outer membrane failureBactericidal Mechanism (Cell Death)
LptD inhibition → LPS accumulation in periplasm → Membrane asymmetry → Cell lysisKey Research: Andolina G et al. (Switzerland, 2018) confirmed LptD binding mechanism via cryo-EM structure. PMID:29540583
Important Limitations
- IV formulation development discontinued due to nephrotoxicity in Phase 3 trials
- Only active against P. aeruginosa (not useful for polymicrobial infections)
- Inhaled formulation still in Phase 3 trials (not yet approved)
- Long-term safety data beyond 28 days of treatment not available
- Resistance mechanisms exist (LptD mutations) though frequency is low
Evidence-Chained Benefits
Evidence-Chained Benefits
Research findings linked to mechanisms and clinical outcomes
What to Expect
Timeline based on observations from published studies. Individual responses may vary.
Based on Phase 1 data: Peak plasma concentrations achieved at end of IV infusion. Inhaled formulation achieves high lung concentrations within minutes of administration.
In clinical trials, bactericidal activity observed within 24-48 hours. Time-dependent killing pattern requires sustained exposure above MIC. Post-antibiotic effect of 1-2 hours noted in vitro.
Phase 2 trials assessed outcomes at test-of-cure visits. Microbiological eradication observed in 50% of patients by day 7. Clinical improvement typically evident within treatment course.
Standard treatment duration in clinical trials was 7-14 days. Nephrotoxicity signal in IV formulation became apparent with prolonged treatment. Inhaled formulation studied up to 28 days.
Research-Based Observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Quality Checklist
Visual indicators to help evaluate Murepavadin product quality
Good Signs (6 indicators)
Warning Signs (5 indicators)
Bad Signs (6 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Peptide Interactions
Known and theoretical interactions when combining Murepavadin with other peptides. Based on published research and mechanistic considerations.
LL-37
CompatibleBoth are antimicrobial peptides with different mechanisms. LL-37 has broad immunomodulatory effects while murepavadin specifically targets P. aeruginosa LptD. No known contraindications.
Lactoferricin
CompatibleDifferent antimicrobial mechanisms. Lactoferricin has membrane-disrupting activity while murepavadin inhibits LPS transport. May have complementary antibacterial effects.
Colistin
CautionBoth target Gram-negative bacteria. Colistin's membrane disruption differs from murepavadin's LptD inhibition. Combined nephrotoxicity risk with IV formulations; monitor renal function.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
References
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
Methodology Note
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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