Danegaptide (ZP1609)_Dosage, benefits & legal status
Also known as ZP1609, ZP-1609, GAP-134, danegaptide hydrochloride
A tiny modified peptide that strengthens the channels linking neighboring cells. It did not protect the heart in a 585-patient trial, and Breye Therapeutics is now taking an oral form into diabetic retinopathy.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Danegaptide (ZP1609)?
Plain language first. The technical label stays, but it never stands alone.Overview
Cells in the heart and in the retina's small blood vessels pass signals to their neighbors through channels called gap junctions, and these links break down under stress such as a heart attack or high blood sugar; danegaptide was made to hold them together. In a 585-patient trial in heart attack patients it did not reduce heart damage (myocardial salvage index, a measure of heart muscle saved, 63.9 and 65.6 against 66.7 on placebo, P=0.40). In a 24-patient open-label oral study in diabetic eye disease, the developer reported good tolerability and less vessel leakage but released no numbers, and a randomized phase 2 is planned for 2027.
Danegaptide is glycyl-(4R)-4-benzamido-L-proline (C14H17N3O4, 291.30 Da), a modified dipeptide that Wyeth and Zealand Pharma disclosed in 2009 as GAP-134, a smaller, orally active successor to Zealand's antiarrhythmic peptide rotigaptide. It stabilizes connexin 43 (Cx43) gap junctions at the cell membrane and increases gap junctional conductance, keeping neighboring heart muscle cells or retinal vascular cells coupled under stress. Zealand's 585-patient phase 2 in heart attack patients undergoing primary PCI showed no reduction in reperfusion injury, and Breye Therapeutics now develops it by mouth for non-proliferative diabetic retinopathy (NPDR) and diabetic macular edema.
What it's used for
Nothing outside trials yet. Breye Therapeutics is developing it as an oral treatment for diabetic retinopathy and diabetic macular edema, after it failed to protect the heart during treatment for heart attacks.
How does Danegaptide (ZP1609) work?
What it does in the body, and where.Danegaptide strengthens gap junctions, the channels that let neighboring cells share signals.
- 01Cells that talkHeart muscle cells and the cells of the retina's blood vessels pass signals to their neighbors through gap junction channels built from a protein called connexin 43.
- 02What stress doesLack of oxygen or high blood sugar makes these junctions uncouple. In the heart this disrupts electrical conduction; in the retina it weakens the barrier between retinal vessel cells and pericytes, and vessels leak.
- 03Holding the linkDanegaptide stabilizes connexin 43 junctions at the cell membrane and increases their conductance. It reduced infarct size in dogs and pigs, but not in people. Carl Regillo, a Breye scientific advisor who presented the eye study, has also said it partly protects against VEGF-induced loss of TNFSF15 and called it a functional VEGF antagonist, a claim not yet tested in a randomized trial.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
Heart attack (phase 2)
tested-and-failed- Human trial585 randomized: myocardial salvage index 63.9 (high dose), 65.6 (low dose) and 66.7 (placebo), P=0.40.
- Human trialFinal infarct size 19.6, 18.6 and 21.4 g (P=0.88); ejection fraction 53.9%, 52.7% and 52.1% (P=0.64); no significant differences in clinical outcomes.
- No dataThe paper gives two per-protocol imaging counts, 243 in the abstract and 169 in the results text; Zealand's release also says 169.
Diabetic eye disease (oral phase 1b)
Investigational- human-early24 patients with NPDR and diabetic macular edema at 11 sites in the UK, Germany and US took 75 to 300 mg a day for 28 days; no dose-limiting toxicities.
- human-earlyExploratory imaging showed less vascular leakage in more than half of study eyes, and edema scores fell significantly by the end of the study.
- No dataOpen-label, with no control group and no numbers released; the presenting investigator, Carl Regillo, is listed among Breye's scientific advisors.
Planned phase 2
Investigational- RegulatoryBreye raised EUR 67.5 million on September 29, 2026, to start a randomized phase 2 in NPDR in 2027; the release gives no size, doses or endpoint, though Breye said in June 2025 that the phase 2 would use the regulatory endpoint of a 2-step or greater improvement on the Diabetic Retinopathy Severity Scale.
Discovery and animal work
Early research- Lab studyFound as dipeptide 9f in a Wyeth and Zealand program for a smaller, orally active successor to rotigaptide.
- Animal studyActive in a mouse model of cardiac conduction block, and described by the authors as orally active.
It is often described simply as a synthetic peptide; it is a modified dipeptide of 291 Da with one non-natural residue, and its current developer and the 2009 Wyeth and Zealand discovery paper call it a small molecule, while Zealand and the Heart authors called it a peptide. It is often reported as a drug that did not translate and was dropped, but only the heart program ended: Breye Therapeutics licensed it in 2022, completed an oral phase 1b in diabetic eye disease in 2025 and raised EUR 67.5 million on September 29, 2026, for a phase 2 starting in 2027. The heart trial randomized 585 patients; the registry lists 591 enrolled. The per-protocol imaging group is given as 243 in the paper's abstract and as 169 in its results text and in Zealand's release.
The published record
Papers and trials about Danegaptide (ZP1609)
11 papers tagged human · 5 not reviews or lab · 2 clinical trial publications
1 registered trials · none with posted results
Furthest stage reached: Published trials only, 2 clinical trial publications, no phased trial registered
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about Danegaptide (ZP1609)
Evidence
Investigational
Category
Healing and recovery
Common vial
Varies
Half-life
Not established
How much, and do you cycle it?
The range, and whether you take breaks.75 mg once daily to 150 mg twice daily for 28 days (phase 1b trial), once or twice daily (phase 1b trial). 28 days of daily dosing in the phase 1b Trial dose
The oral study gave it every day for 28 days, and the heart trial gave one bolus and a 6-hour infusion. How long treatment would last in diabetic retinopathy is not yet established.
Not establishedNo figure
No human half-life has been published: the Heart paper says the phase 1 pharmacokinetic data were not published, and Breye has said only that the phase 1b reached its target exposures. At the end of PCI in the heart trial, plasma levels were 451 ± 369 ng/mL on the high dose and 141 ± 48.4 ng/mL on the low dose, closely reflecting the dose. Oral bioavailability in people has not been reported.
Source: Engstrøm T et al., Heart 2018 (phase 1 pharmacokinetic data not published)
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What does it cost?
Typical dose and cost, in plain numbers.Danegaptide (ZP1609) is not injected
It is taken by mouth (oral). Taken by mouth for 28 days in the phase 1b, in four rising-dose groups: 75 mg once daily, 75 mg twice daily, 150 mg once daily and 150 mg twice daily (75 to 300 mg a day). Doses for the planned phase 2 have not been disclosed. The earlier heart attack trial gave it into a vein at fixed doses, 2.5 mg as a bolus and then 7.5 mg over 6 hours, or 7.5 mg and then 22.5 mg over 6 hours, starting at least 10 minutes before the blocked artery was opened (PCI). No product exists outside trials, so the calculator starts with an empty dose field.
How do you store it?
Before mixing, and after.Room temperature. Cool, dry, out of light.
Danegaptide (ZP1609) is taken as a pill or capsule. Keep it in its original container at room temperature, away from heat, humidity, and direct sun. No fridge or mixing needed. Check the expiration date on the bottle.
What are the side effects and cautions?
Known cautions and warnings for this compound.Who should avoid it
- Not studied in pregnancy or breastfeeding: no data exist
- Not studied in children: the heart trial enrolled adults 18 and older
- Not studied by mouth for longer than 28 days: the oral phase 1b lasted 4 weeks
- Not studied in heart attack patients with cardiogenic shock or after clot-dissolving treatment: both were excluded from the heart trial
- Use outside a trial: it is not approved, and what is sold online is a research chemical, not a medical product
Stop and get help
- Chest pain, fainting or a racing or irregular heartbeat: it acts on the gap junctions that carry the heart's electrical signal
- Sudden blurring or loss of vision, a sign of worsening diabetic eye disease that needs prompt eye care
Common effects
- In the heart attack trial, the authors reported few side effects and no difference from placebo in adverse events, serious adverse events or deaths
- Death from any cause 1.6% (high dose) and 1.5% (low dose) against 2.1% on placebo (P=0.90); reinfarction by 90 days 0.5% and 1.0% against 1.0%
- Heart failure 7.1% and 4.9% against 4.1% on placebo (P=0.44), not a significant difference
- In the 28-day oral eye study (24 patients), no dose-limiting toxicities from 75 mg once daily to 150 mg twice daily
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Danegaptide (ZP1609) approved?
And where the numbers on this page come from.No. Danegaptide (ZP1609) is not approved anywhere and is currently in company-run clinical trials. There is no legal route to obtain it outside a trial.
- Approval statusInvestigational
- RouteBy mouth (oral)
- Checked21 October 2026
- DoseFrom published clinical trials. Not approved by a regulator for this dose.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesEngstrøm T et al., Heart 2018;104:1593-1599Engstrøm T et al., Heart 2018, full textClinicalTrials.gov, NCT01977755Zealand Pharma, phase 2 results (Fierce Biotech, March 2, 2016)FDA GSRS substance record, danegaptide (UNII PA0Y7735AT)Butera et al., Journal of Medicinal Chemistry 2009;52:908-911Novo Holdings, Breye Therapeutics launch (November 10, 2022)Breye Therapeutics, Series A (September 29, 2026)NHS Health Research Authority, phase 1b summaryOphthalmology Times, phase 1b completed (June 25, 2025)The Ophthalmologist, Could NPDR be treated orally? (March 2026)MedPath, Breye Series A (2026)
What has happened recently
Never approved anywhere, and no orphan, fast track or breakthrough designation has been reported. Danegaptide came out of a Zealand Pharma peptide library in a collaboration with Wyeth, as a smaller, orally active successor to rotigaptide, and its structure was published as GAP-134 in 2009; Wyeth began phase 1 testing in healthy volunteers in 2007 under the partnership, including an oral formulation, and those results were never published, and Pfizer acquired Wyeth in 2009. Zealand ran a phase 2 in heart attack patients at Rigshospitalet in Copenhagen, enrolling from November 2013 to August 2015, and on March 2, 2016, announced that it had no effect on myocardial salvage, saying it would focus its resources on its proprietary pipeline; heart development ended there. Breye Therapeutics of Copenhagen in-licensed it from Zealand and launched on November 10, 2022, with EUR 4 million in seed funding from Novo Holdings and Sound Bioventures. Breye reported completing an oral phase 1b in diabetic macular edema on June 25, 2025, and on September 29, 2026, raised a EUR 67.5 million Series A, co-led by Mission BioCapital and Novo Holdings, to start a randomized phase 2 in non-proliferative diabetic retinopathy in 2027.
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What else is like Danegaptide (ZP1609)?
Others in Healing and recovery, side by side.If you're weighing Danegaptide (ZP1609), it's worth reading Dolcanatide (SP-333), Serelaxin (RLX030), and BPC-157 in the same class.
A tiny modified peptide that strengthens the channels linking neighboring cells. It did not protect the heart in a 585-patient trial, and Breye Therapeutics is now taking an oral form into diabetic retinopathy.
- Dose
- 75 mg once daily to 150 mg twice daily for 28 days (phase 1b trial)
- How often
- Once or twice daily (phase 1b trial)
The same atoms as plecanatide, with the first and last amino acids switched to their mirror-image forms to resist digestion. It reached phase 2 for opioid-induced constipation; Bausch Health bought it in 2019 and has reported no development since 2020.
- Dose
- 3 or 6 mg once daily (phase 2 trial)
- How often
- Once daily (phase 2 trial)
Recombinant human relaxin-2, a two-chain hormone that relaxes arteries, given as a 48-hour drip in acute heart failure. In RELAX-AHF-2 cardiovascular deaths were 8.7% against 8.9% on placebo, and Novartis ended development in 2017.
- Dose
- 30 mcg/kg per day by continuous infusion for 48 hours (phase 3 trials)
- How often
- Once, as a single 48-hour infusion
A popular healing peptide for injuries, gut, and joint or tendon pain.
- Dose
- 0.25 up to 0.5 mg per dose (start low, increase slowly)
- How often
- 1-2x daily
Guides for this compound
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- Engstrøm T et al., Heart 2018;104:1593-1599(2018)585 randomized (184 high dose, 206 low dose, 195 placebo); myocardial salvage index 63.9, 65.6 and 66.7 (P=0.40); infarct size (P=0.88) and LVEF (P=0.64) did not differ.
- Engstrøm T et al., Heart 2018, full text(2018)IV doses; plasma levels 451 and 141 ng/mL at the end of PCI; clinical events by arm; phase 1 pharmacokinetic data not published.
- ClinicalTrials.gov, NCT01977755(2018)Three arms with an IV bolus and 6-hour infusion; single site in Copenhagen; 591 listed as enrolled; no results posted.
- Zealand Pharma, phase 2 results (Fierce Biotech, March 2, 2016)(2016)No effect on myocardial salvage in the 169 patients who qualified for cardiac MRI; resources refocused on the proprietary pipeline.
- FDA GSRS substance record, danegaptide (UNII PA0Y7735AT)(2026)Glycyl-(4R)-4-(benzoylamino)-L-proline; C14H17N3O4, MW 291.30; CAS 943134-39-2; stabilizes Cx43 gap junctions to enhance coupling.
- Butera et al., Journal of Medicinal Chemistry 2009;52:908-911(2009)Discovery of GAP-134, an orally active gap-junction modifier and dipeptide derived from the rotigaptide work.
- Novo Holdings, Breye Therapeutics launch (November 10, 2022)(2022)In-licensed from Zealand; EUR 4 million seed; described as an oral small molecule tested in more than 500 people.
- Breye Therapeutics, Series A (September 29, 2026)(2026)EUR 67.5 million raised; randomized phase 2 in NPDR to start in 2027; phase 1b well tolerated at all dose levels.
- NHS Health Research Authority, phase 1b summary(2023)Open-label dose escalation by mouth, 75 mg once daily to 150 mg twice daily for 28 days; ISRCTN13284995.
- Ophthalmology Times, phase 1b completed (June 25, 2025)(2025)24 patients at 11 sites; no dose-limiting toxicities; target exposures reached; phase 2 endpoint on the Diabetic Retinopathy Severity Scale.
- The Ophthalmologist, Could NPDR be treated orally? (March 2026)(2026)Less vascular leakage in more than half of study eyes, presented February 7, 2026; no numeric effect sizes.
- MedPath, Breye Series A (2026)(2026)Wyeth phase 1 in 2007 and Pfizer's 2009 purchase of Wyeth; Breye's CEO was Zealand's head of clinical development. Secondary source.
Beyond these, 31 records are indexed. Browse the records