αCT1 (Alpha Connexin Carboxyl-Terminus 1)
A cell-penetrating peptide built from the tail of connexin43 that retunes gap junctions in healing skin — tested as the gel Granexin for ulcers and scars. Investigational, not an approved drug
alphaCT1 (also written aCT1 or ACT1, and formulated as the gel Granexin) is a 25-amino-acid peptide designed to work on the body's gap junctions — the channels that let neighbouring cells share small signalling molecules. It copies the last nine amino acids of connexin43, the main gap-junction protein of skin and heart, and attaches them to a short 'cell-penetrating' tag so the peptide can get inside cells. There it binds a scaffolding protein called ZO-1 and blocks it from grabbing connexin43, which reorganises gap junctions, calms the early inflammatory response to a wound, and steers healing toward regeneration rather than scar. In human randomised trials the topical gel improved the healing of chronic venous leg ulcers and diabetic foot ulcers and, in a Phase I study, produced surgical scars whose collagen looked more like unwounded skin. The results have been mixed at the pivotal stage, though: a large US Phase 3 diabetic-foot trial (GAIT-1) was terminated, while a Phase 2b/3 scar trial completed and eye-drop (dry-eye) and other programmes were explored. alphaCT1 is an investigational medicine applied as a topical gel in trials; it is not approved in any country, and this page records the published science, not a how-to.
No established human dose Details ↓
Recommended Dosing
No established human dose
alphaCT1 has been given to people only inside clinical trials, as an investigational topical gel (Granexin) or eye drop (iNexin) applied under study supervision — for example Granexin gel at 100-200 micromolar in the surgical-scar trial (ClinicalTrials.gov NCT04331080) and 0.08-2.0% alphaCT1 eye drops in a dry-eye study (NCT05031806). Those are trial formulations tied to their protocols, not a self-administration dose: there is no approved product, no established regimen, and no amount is printed here as guidance.
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What is it?
Gap junctions are clusters of channels that directly connect the insides of neighbouring cells, and their most widespread building block is the protein connexin43 (Cx43). When skin is wounded, Cx43 behaviour at the wound edge changes, and both laboratory and clinical observations have linked persistently high Cx43 to poor, slow, scar-prone healing. alphaCT1 was built to intervene at exactly that point: it is a short synthetic peptide that reproduces the final nine amino acids of the Cx43 tail — the part that carries a 'PDZ-binding' motif — joined to a cell-penetrating antennapedia sequence so it can cross into cells.
Inside the cell, alphaCT1's Cx43 tail competes for the PDZ2 domain of zonula occludens-1 (ZO-1), a scaffolding protein that normally tethers Cx43 at the edges of gap-junction plaques. By occupying ZO-1, alphaCT1 loosens the Cx43/ZO-1 grip, which lets gap-junction channels aggregate differently and shifts the wound response. In animal skin wounds this reduces the early neutrophil (inflammatory) surge, shrinks the zone of scar-forming tissue, and restores more normal dermal structure and mechanical strength — a move toward regeneration rather than fibrosis.
alphaCT1 reached human testing as a topical gel (Granexin). In a multicentre randomised trial in chronic venous leg ulcers, adding the gel to standard compression care gave a significantly greater reduction in ulcer area at 12 weeks than standard care alone; a separate multicentre randomised trial in chronic neuropathic diabetic foot ulcers found the same pattern, with faster time to complete closure and no treatment-related adverse events or immune reaction. A later human study of surgical wounds showed that alphaCT1-treated scars laid down collagen in a less-aligned pattern that more closely resembles unwounded skin — a tissue correlate of the improved scar appearance reported in Phase II scar testing.
The late-stage picture is mixed, which is why this peptide is still investigational. A pivotal US Phase 3 trial of Granexin gel in diabetic foot ulcers (GAIT-1) was terminated; a Phase 2b/3 scar trial after breast surgery completed; a dry-eye eye-drop formulation (iNexin) and other indications were explored, and a planned burn-wound trial was withdrawn before enrolment. The same Cx43/ZO-1 mechanism has also been studied in the heart, where the peptide reduced gap-junction remodelling and inducible arrhythmia after experimental ventricular injury in mice, and in the eye and brain vasculature.
alphaCT1 is an investigational peptide, not an approved medicine. It has been given to people only inside clinical trials, as a topical gel or eye drop applied under study supervision; it is approved nowhere, there is no established self-administration dose, and material sold online under peptide names is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records what the published trials and studies report.
Mechanism of Action
alphaCT1 is a 25-amino-acid cell-penetrating peptide that reproduces the connexin43 carboxyl-terminus and blocks its interaction with the scaffolding protein ZO-1. By remodelling gap junctions and calming the early wound inflammatory response, it shifts healing toward regeneration and away from scar.
Cx43/ZO-1 blockade
alphaCT1's Cx43 C-terminal motif binds the PDZ2 domain of ZO-1, displacing ZO-1 from connexin43 and reorganising gap-junction plaques (PMID 21273554); its antennapedia tag carries it into cells (PMID 23876491 describes the 25-residue design).
Regenerative wound healing
In skin wounds the peptide lowers the early neutrophil surge, shrinks scar-progenitor tissue and restores dermal structure (PMID 19317641), and in people improves ulcer re-epithelialisation (PMIDs 25072595, 25703647) and scar collagen architecture (PMID 34246197).
Cardiac gap-junction stabilisation
After experimental ventricular injury the same mechanism preserved Cx43 at intercalated disks and reduced inducible arrhythmia via PKC-epsilon-driven Cx43 serine-368 phosphorylation (PMID 21273554) — a separate preclinical application.
Published Research
These are studies of alphaCT1 (the connexin43 carboxyl-terminal mimetic peptide, gel name Granexin) read from their PubMed records on November 7, 2026. They include two multicentre human randomised trials in chronic wounds (venous leg ulcers and diabetic foot ulcers), a human Phase I surgical-scar study with supporting animal and computational models, a review of connexin43-based wound-healing therapeutics, and animal studies of the peptide's effects on cardiac gap junctions/arrhythmia and on skin scarring. Development is investigational, and late-stage results have been mixed (a pivotal Phase 3 diabetic-foot trial was terminated).
Connexin43-based peptide heals chronic venous leg ulcers (RCT)
In a prospective multicentre randomised trial in India, adults with chronic venous leg ulcers received the connexin43-based peptide ACT1 as a gel plus standard compression care, or standard care alone. Adding ACT1 gave a significantly greater reduction in mean ulcer area at 12 weeks (79% vs 36%; p=0.02) and a shorter time to 50% and 100% re-epithelialisation — a positive human interventional result in chronic wound healing.
Topical connexin43-based peptide augments diabetic foot ulcer healing (RCT)
A prospective multicentre randomised trial tested the connexin43 C-terminal peptide ACT1, added to standard of care, in adults with chronic neuropathic diabetic foot ulcers. ACT1 was associated with a significantly greater reduction in mean ulcer area over 12 weeks (72.1% vs 57.1%; p=0.03), a higher proportion reaching full closure and a shorter median time to closure, with no treatment-related adverse events and no detectable immunogenicity — a positive human interventional result.
alphaCT1 makes surgical-scar collagen resemble unwounded skin (Phase I + models)
Building on Phase II data that acute alphaCT1 improved surgical scar appearance by about 47% at 9 months, this study compared alphaCT1- and vehicle-treated wounds within the same patients (Phase I biopsies at day 29) and in rat and guinea-pig models. The main effect on scar structure was that alphaCT1-treated scars had less-aligned collagen fibres — a feature of unwounded skin — explained by alphaCT1 reducing the directionality of fibroblast movement (a human clinical-trial study with supporting animal and computational models).
Connexin 43-based therapeutics for dermal wound healing
A review of connexin43 as a target in skin wound healing. It summarises that local knockdown of Cx43, and Cx43-based peptides such as alphaCT1 (a mimetic of the Cx43 carboxyl terminus), improve wound closure and scar appearance in preclinical and clinical work, and notes that Phase III testing of alphaCT1 for diabetic foot ulcers was underway — framing connexin-targeted therapeutics as a promising route to modulate the body's healing response.
Connexin43 carboxyl-terminus peptide reduces gap-junction remodelling and arrhythmia (mouse heart)
In a mouse model of left-ventricular cryoinjury, the Cx43 carboxyl-terminal mimetic alphaCT1, released locally from a patch, reduced Cx43/ZO-1 co-localisation, preserved Cx43 at intercalated disks in the injury border zone, lowered inducible arrhythmia and raised ventricular depolarisation rate. The effect was linked to increased Cx43 phosphorylation at serine-368 via protein kinase C-epsilon — a preclinical cardiac result for the same gap-junction mechanism.
Connexin43 carboxyl-terminal peptide reduces scarring and promotes regeneration (skin)
In mouse and pig models of skin wounding, a cell-permeant peptide from the Cx43 carboxyl terminus (the basis of alphaCT1) reduced the area of scar-progenitor tissue and restored more normal dermal structure and mechanical strength, preceded by a fall in inflammatory neutrophil infiltration and a change in epidermal Cx43 organisation — an early preclinical demonstration of regenerative, lower-scar healing that motivated the clinical programme.
No Established Human Dose
alphaCT1 has been given to people only inside clinical trials, as an investigational topical gel (Granexin) or eye drop (iNexin) applied under study supervision — for example Granexin gel at 100-200 micromolar in the surgical-scar trial (ClinicalTrials.gov NCT04331080) and 0.08-2.0% alphaCT1 eye drops in a dry-eye study (NCT05031806). Those are trial formulations tied to their protocols, not a self-administration dose: there is no approved product, no established regimen, and no amount is printed here as guidance.
What this rests on: PMID 25072595, PMID 25703647, PMID 34246197.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes αCT1 (Alpha Connexin Carboxyl-Terminus 1) is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of αCT1 (Alpha Connexin Carboxyl-Terminus 1) has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store αCT1 (Alpha Connexin Carboxyl-Terminus 1), before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long αCT1 (Alpha Connexin Carboxyl-Terminus 1) stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking αCT1 (Alpha Connexin Carboxyl-Terminus 1). What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of short; rapid metabolism of the free peptide is reported, motivating sustained-release and gel formulations. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for αCT1 (Alpha Connexin Carboxyl-Terminus 1). Results reported in the studies are under Published Research.
Source: half-life: PMID 23876491.
Side effects, and when to stop or get help
From the Side Effects section: In the diabetic foot ulcer randomised trial, no adverse events were reported as treatment-related and the peptide was not immunogenic (PMID 25703647); The venous leg ulcer randomised trial likewise reported the gel as well tolerated alongside standard care (PMID 25072595); Human safety data are limited to topical use in trials; a pivotal Phase 3 diabetic-foot trial was terminated, so late-stage efficacy and safety in that setting are not established (ClinicalTrials.gov NCT02667327); There is no established safety profile for any non-topical or self-directed use; material sold online under peptide names is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping αCT1 (Alpha Connexin Carboxyl-Terminus 1). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“alphaCT1 is investigational; the safety information below comes from the clinical trials carded here, where it was applied topically under supervision”).
Interactions
Unknown: a PubMed search for human interaction studies of αCT1 (Alpha Connexin Carboxyl-Terminus 1) (reviewed 2026-11-07) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of αCT1 (Alpha Connexin Carboxyl-Terminus 1) products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: In Clinical Trials (Investigational, not approved: Drugs@FDA and the openFDA label endpoint hold no approved application or label for αCT1 / Granexin (searched November 7, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
alphaCT1 is investigational; the safety information below comes from the clinical trials carded here, where it was applied topically under supervision. It is not an approved product and has no consumer safety profile.
Contraindications & Cautions
alphaCT1 has no approved use and no drug label. These points reflect its investigational status.
Legal Status
alphaCT1 (Granexin) is an investigational topical peptide studied in clinical trials; it is not an approved drug in any country.
Frequently Asked Questions
?What is alphaCT1?
A 25-amino-acid synthetic peptide (also written aCT1 or ACT1, gel name Granexin) that copies the last nine amino acids of connexin43 — a gap-junction protein — joined to a cell-penetrating tag. It blocks connexin43 from binding the scaffolding protein ZO-1, remodelling gap junctions in healing tissue.
?What is it used for in research?
Mainly wound healing and scar reduction. Human randomised trials tested the topical gel in chronic venous leg ulcers and diabetic foot ulcers (PMIDs 25072595, 25703647), and a human study showed it improves surgical-scar collagen (PMID 34246197). The same mechanism has been studied in the heart and eye.
?Does it work?
Results are mixed. Phase II randomised trials were positive for ulcer healing and scar appearance, but the pivotal US Phase 3 diabetic-foot trial (GAIT-1) was terminated and a scar trial completed, so alphaCT1 remains investigational rather than proven (ClinicalTrials.gov NCT02667327, NCT04331080).
?Is it approved or available to buy?
No. alphaCT1/Granexin is not approved in any country; it has been given to people only in clinical trials as a topical gel or eye drop. Material sold online under peptide names is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source.
References
- [rct] Ghatnekar GS, et al. "The effect of a connexin43-based Peptide on the healing of chronic venous leg ulcers: a multicenter, randomized trial." J Invest Dermatol, 2015;135(1):289-298. PMID: 25072595.
- [rct] Grek CL, et al. "Topical administration of a connexin43-based peptide augments healing of chronic neuropathic diabetic foot ulcers: A multicenter, randomized trial." Wound Repair Regen, 2015;23(2):203-12. PMID: 25703647.
- [clinical-trial] Montgomery J, et al. "The connexin 43 carboxyl terminal mimetic peptide αCT1 prompts differentiation of a collagen scar matrix in humans resembling unwounded skin." FASEB J, 2021;35(8):e21762. PMID: 34246197.
- [review] Montgomery J, et al. "Connexin 43-Based Therapeutics for Dermal Wound Healing." Int J Mol Sci, 2018;19(6). PMID: 29914066.
- [animal] O'Quinn MP, et al. "A peptide mimetic of the connexin43 carboxyl terminus reduces gap junction remodeling and induced arrhythmia following ventricular injury." Circ Res, 2011;108(6):704-15. PMID: 21273554.
- [animal] Ghatnekar GS, et al. "Connexin43 carboxyl-terminal peptides reduce scar progenitor and promote regenerative healing following skin wounding." Regen Med, 2009;4(2):205-23. PMID: 19317641.
- [other] UniProt P17302 (CXA1_HUMAN, gene GJA1), read November 7, 2026: connexin43 is the gap-junction alpha-1 protein. alphaCT1 is a synthetic 25-residue peptide that reproduces the nine C-terminal amino acids of connexin43 (which carry a PDZ-binding motif) fused to a cell-penetrating antennapedia internalisation sequence; it is not itself a gene product. https://www.uniprot.org/uniprotkb/P17302/entry
- [other] alphaCT1 was designed by Robert Gourdie and colleagues as a mimetic of the connexin43 carboxyl-terminus that binds the PDZ2 domain of zonula occludens-1 (ZO-1), blocking the Cx43/ZO-1 interaction and remodelling gap junctions; it was developed as the topical gel Granexin by FirstString Research and then Xequel Bio (naming the developer/sponsor only; Grey Peptides lists no seller). The peptide's design and mode of action are described in the review and mechanism studies carded on this page (read November 7, 2026).
- [other] ClinicalTrials.gov, searched November 7, 2026 (sponsor Xequel Bio, Inc.): Granexin gel (alphaCT1) was tested in a completed Phase 2b/3 within-subject trial of scar formation after bilateral breast surgery at 100 and 200 micromolar (NCT04331080); a pivotal US Phase 3 diabetic-foot-ulcer trial, GAIT-1, was TERMINATED (NCT02667327); Phase 1 pharmacokinetic studies in diabetic foot ulcers (NCT02652754) and venous leg ulcers (NCT02652572) completed; an alphaCT1 eye-drop formulation (iNexin, 0.08-2.0%) completed a Phase 1 dry-eye study (NCT05031806); and a Phase 2 burn-wound trial was withdrawn with no enrolment (NCT04684121). https://clinicaltrials.gov/
- [other] US FDA, Drugs@FDA and the openFDA label endpoint, searched November 7, 2026: no approved application and no drug label for alphaCT1 / Granexin. It is an investigational topical peptide that has been studied in clinical trials but is not approved in the United States; FDA GSRS lists the substance without any approval.
Sources & Citations
The six studies carded above were read from their PubMed records on November 7, 2026. Identity comes from UniProt (P17302, connexin43); alphaCT1's design as a Cx43 carboxyl-terminal mimetic that blocks Cx43/ZO-1, its wound-healing and scar effects, and its cardiac and skin preclinical data are from the review and studies carded here. Clinical development (the venous-leg-ulcer and diabetic-foot-ulcer randomised trials, the Phase I scar study, the completed Phase 2b/3 scar trial NCT04331080, the terminated Phase 3 diabetic-foot trial GAIT-1 NCT02667327, and the iNexin dry-eye study NCT05031806) was checked on ClinicalTrials.gov the same day, as was the absence of US approval via Drugs@FDA and openFDA. The developer (FirstString Research, later Xequel Bio) is named for context only; Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.