Murepavadin
InvestigationalA 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.
POL7080 · RG7929
18 human studies
- Preclinical
- 36%
- Clinical
- 64%
Based on 28 cited sources
Demonstrated effect magnitude — not a recommendation or safety claim.
Research Depth 60 (1A 25: best published human evidence is small double-blind placebo-controlled Phase 1 PK/safety RCTs 29437621/30012756, n<50 per cohort; no published efficacy data — Phase 3 IV HABP/VABP program halted for nephrotoxicity 31554212, inhaled Phase 3 unreported; 1B 14 low-RoB on PK/safety only; 1C 6 total human N ~100-300; 1D 7 PK surrogate, right population but efficacy outcome never read out; 1E 8 substantial multi-model preclinical program). Mechanism 95 (2A 40: LptD target confirmed by binding + photo- crosslinking 29359918 and resistance/WGS lptD mutations 33367642; 2B 28 full LptD->LPS-transport-block->membrane-failure->lysis chain; 2C 17 MIC dose- response plus in-vivo AUC/MIC PK/PD index 30642931; 2D 10 confirmed in mouse models). Plausibility 77 (3A 26: mechanism->bactericidal surrogate established, surrogate->clinical cure inferred only; 3B 23 coherent with LPS-transport biology; 3C 14 anti-pseudomonal class analogy though first-in-class OMPTA; 3D 14 tightly scoped narrow-spectrum claim). Global Coverage 65 (4A 24 replicated by independent groups — JMI/US 29901750, Radboud-Erasmus/NL 30642931, Ramon y Cajal/ES 33367642, Emory/US 31554212 — beyond Zurich/Polyphor origin; 4B 20 many countries; 4C 16 ~20-30 study literature; 4D 5 investigational, trial-registered, never approved). Community Experience 5: investigational antibiotic with no documented real-world/community use. Effectiveness not-established: no quantified human efficacy estimate (Phase 3 IV halted pre-readout, inhaled Phase 3 pending) and no meaningful community effect signal.
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 photo-crosslinking work that localized its binding site on LptD.
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.
Key Research: Andolina G et al. (Switzerland, 2018) mapped the LptD binding site using photo-crosslinking and mass-spectrometry-based proteomics, localizing the interaction to the Pseudomonas-specific periplasmic segment of LptD. PMID:29359918
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
Based on Phase 1 data: peak plasma concentrations are achieved at the end of the IV infusion, with a geometric mean half-life of roughly 2.5-5.3 h and dose-proportional, linear pharmacokinetics.
PMID:29437621In vitro, murepavadin is bactericidal against most P. aeruginosa strains within 1-5 hours at higher concentrations, consistent with sustained exposure above the MIC.
PMID:33367642Exposure to murepavadin increases in renal impairment (AUC roughly 2- to 2.5-fold higher), so the elimination half-life lengthens over a multi-day course and dose adjustment is warranted with reduced renal function.
PMID:30012756With prolonged IV treatment, a nephrotoxicity signal led to discontinuation of the Phase 3 IV program; development has since focused on the inhaled formulation.
PMID:31554212Research-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.
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.
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.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
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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