C6 Peptide — Preclinical research guide.
C6 is a short synthetic peptide designed to block Hv1 voltage-gated proton channels in neutrophils — the white blood cells that drive the runaway inflammation seen in Acute Respiratory Distress Syndrome (ARDS). In mouse models it suppressed lung inflammation from both sterile injury and live bacterial infection.
- Synthetic peptide inhibitor of Hv1 (HVCN1), a voltage-gated proton channel neutrophils rely on to generate their inflammatory oxidative burst.
- Suppresses release of reactive oxygen species, proteases and inflammatory cytokines from activated neutrophils.
- Reduced lung injury and neutrophil infiltration in LPS-induced and live Pseudomonas aeruginosa-induced mouse models of acute lung injury.
- Also active on human neutrophils in vitro, blocking the same Hv1-dependent inflammatory pathway seen in the mouse studies.
- Developed by researchers at UC Irvine and UCLA; preclinical stage only — not manufactured or sold commercially.
What is the C6 peptide?
The C6 peptide is a synthetic inhibitor designed to block Hv1 (also called HVCN1), a voltage-gated proton channel expressed on neutrophils and other immune cells. Hv1 helps neutrophils generate the burst of reactive oxygen species they use to kill pathogens, but in Acute Respiratory Distress Syndrome (ARDS) and its milder form Acute Lung Injury (ALI), that same mechanism becomes self-destructive: neutrophils flood the lungs, and their oxidative burst, combined with released proteases and cytokines, damages the delicate alveolar-capillary barrier and floods the lungs with fluid.
How does it work?
By blocking Hv1, C6 limits the ability of neutrophils to sustain the proton flux their NADPH-oxidase system needs to generate reactive oxygen species. In practice this dampens the release of ROS, proteolytic enzymes and pro-inflammatory cytokines from activated neutrophils, without eliminating the cells outright. Researchers designed C6 specifically as a targeted alternative to broader immunosuppressants, aiming to blunt the damaging part of the neutrophil response while leaving normal antimicrobial defence more intact.
What does the research show?
In an LPS-induced mouse model of acute lung injury, intravenous C6 reduced neutrophil accumulation, reactive oxygen species and pro-inflammatory cytokines in bronchoalveolar lavage fluid. A follow-up study extended this to a live bacterial-infection model — Pseudomonas aeruginosa-induced lung injury — where C6 again suppressed neutrophil migration into the lungs and reduced multiple inflammatory cytokines linked to ARDS severity, including IL-6 and IL-8. C6 also inhibited Hv1 in human neutrophils in vitro, and researchers reported no apparent toxic side effects in the treated mice. All efficacy data to date comes from mouse models and in vitro human cell work; no human clinical trials have been conducted.
Is the C6 peptide available for research or purchase?
No. C6 is an academic discovery from research groups at UC Irvine and UCLA, first described in 2018 and refined in subsequent studies. It is not commercially manufactured, has no assigned CAS number, and there is no research-peptide vendor offering it for sale. It's included here as a scientific reference point for ARDS/ALI research, not as a sourcing option.