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A specimen of the Immune drawer Drawer F · Immune

Murepavadin

Investigational

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.

POL7080 · RG7929

Research evidence
Moderate

18 human studies

Preclinical
36%
Human research
64%

Based on 28 cited sources

Numeric assessment unreviewed

A historical numeric score is recorded but has not passed a current, compound-specific assessment review. No numeric score is displayed.

This is a limitation of the numeric assessment, not a measured absence of benefit. It does not re-review the separately recorded catalogue classification or establish efficacy or safety.

Scoring context and limitations
~
Evidence Level
moderate
Clinical trials for Pseudomonas aeruginosa infections.
Investigational
Identity
SCALE · 1:1 N-TERMINUS C-TERMINUS 14 AA · 1,885 Da
Also Known As
POL7080 • RG7929
Class
Cyclic peptidomimetic
Length
14 amino acids
Mol. weight
1,885 Da
Sequence
Cyclic beta-hairpin (proprietary)
Molecular Structure
DPro
Pro
Arg
Arg
Tyr
Arg
Val
Trp
Cys
Arg
Arg
Tyr
Phe
Cys
Hydrophobic
Polar
Positive
Negative

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:

LptD Binding

Binds to the N-terminal plug domain of LptD, the outer membrane protein that inserts lipopolysaccharide (LPS) into the bacterial membrane.

LPS Transport Block

Locks LptD in a non-functional conformation, preventing new LPS from being inserted into the outer membrane.

Membrane Disruption

Without new LPS, the bacterial outer membrane loses integrity and becomes asymmetric, leading to cell death.

Species Selectivity

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
i. Lpt Transport Pathway · LPS Assembly
LPS synthesis (inner membrane)LptBFGC (ABC transporter)LptA (periplasm)Murepavadin ⟶ LptDE (blocked) ⟶ X No LPS insertionOuter membrane failure
ii. Bactericidal Mechanism · Cell Death
LptD inhibitionLPS accumulation in periplasmMembrane asymmetryCell lysis
Mechanism LptD inhibition blocking lipopolysaccharide transport to outer membrane
Established 8 direct studies
Benefit shown to kill Pseudomonas aeruginosa bacteria
Evidence Level
Moderate
3 Human
4 Animal
6 In Vitro
Mechanism Disruption of outer membrane integrity via LPS depletion
Established 5 direct studies
Benefit appears to treat drug-resistant P. aeruginosa infections
Evidence Level
Moderate
2 Human
3 Animal
4 In Vitro
Mechanism Species-specific targeting of P. aeruginosa LptD protein structure
Established 4 direct studies
Benefit may preserve beneficial microbiome during treatment
Evidence Level
Low
1 Human
2 Animal
3 In Vitro
Mechanism High local concentration delivery via inhaled formulation
Supported 3 direct studies
Benefit appears to reduce systemic toxicity while maintaining efficacy
Evidence Level
Low
1 Human
2 Animal
Mechanism Confidence
Established
Supported
Emerging
Evidence Level
High
Moderate
Low
Very Low
Phase 01 1
Hours 1-6

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:29437621
Phase 02 2
Days 1-3

In vitro, murepavadin is bactericidal against most P. aeruginosa strains within 1-5 hours at higher concentrations, consistent with sustained exposure above the MIC.

PMID:33367642
Phase 03 3
Days 3-7

Exposure 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:30012756
Phase 04 4
Days 7-14

With prolonged IV treatment, a nephrotoxicity signal led to discontinuation of the Phase 3 IV program; development has since focused on the inhaled formulation.

PMID:31554212

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.

Synergistic
Compatible
Caution
Avoid

LL-37

Compatible
Compatible

Both are antimicrobial peptides with different mechanisms. LL-37 has broad immunomodulatory effects while murepavadin specifically targets P. aeruginosa LptD. No known contraindications.

Lactoferricin

Compatible
Compatible

Different antimicrobial mechanisms. Lactoferricin has membrane-disrupting activity while murepavadin inhibits LPS transport. May have complementary antibacterial effects.

Colistin

Caution
Caution

Both 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.

28 Sources 18 Human 10 Preclinical

Key Studies Cited

In Vitro Srinivas N et al. 2010
PMID:20167788
In Vitro Sader HS et al. 2018
PMID:29901750
Review Martin-Loeches I et al. 2018
PMID:29451043
Animal Melchers MJ et al. 2019
PMID:30642931
In Vitro Andolina G et al. 2018
PMID:29359918
In Vitro Díez-Aguilar M et al. 2021
PMID:33367642

Use the source links in the research discussion above to inspect the referenced records.

This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength labels summarize the cited material for this entry and should be read alongside its population, model, and study limitations.

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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Compare Murepavadin

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3 entries