Modimelanotide
A lysine-tipped copy of alpha-MSH, infused around heart surgery to spare the kidneys, that failed its decisive trial
Modimelanotide is the international name for AP214, later ABT-719: the skin and immune hormone alpha-MSH with a string of six lysines added to its front end. It was built to carry alpha-MSH's anti-inflammatory effect into the kidney, which is injured in roughly 5 to 30 percent of patients after heart surgery, by the phase 2b paper's count. In mice and pigs it protected kidneys from sepsis and from blood-flow interruption. In people it was given as short intravenous infusions on the day of the operation and the days after. A Danish trial of 77 patients looked encouraging, but the larger 240-patient trial that followed found the same rate of kidney injury on all three doses as on placebo, and the drug's owner stopped a second trial two months later. It was never approved anywhere.
Used in human trials: 800 µg/kg in total (200, 400, 200 µg/kg), Before incision, at aortic clamp release, 6 hours later, Intravenous infusion over 10 minutes (Study: phase 2b, lowest dose arm) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Alpha-MSH is a 13-amino-acid hormone cut from the same precursor protein as ACTH. It is best known for darkening skin, but it also calms inflammation, and through the 1990s kidney researchers found that it shielded mouse and rat kidneys when their blood supply was cut off and restored, even when it was given six hours after the injury (those papers are listed under References). Natural alpha-MSH is short-lived and its effects are hard to pin to one receptor, so the Danish company Action Pharma made a modified version for clinical use. AP214, now called modimelanotide, keeps the whole alpha-MSH chain and adds six lysines at its front end, a change the company's papers describe as raising its affinity for melanocortin receptors.
The clinical target was acute kidney injury after cardiac surgery. When a heart operation runs on a bypass pump, the kidneys go through a spell of reduced and altered blood flow, then a surge of inflammatory signals as circulation returns. Many patients come out of surgery with a rise in creatinine, and that rise is tied to longer stays and higher death rates later. No drug is approved to prevent it, and a long list of candidates has failed. A melanocortin agonist that damps the inflammatory surge was a reasonable idea to test, and the timing was easy to control: the operation is scheduled, so the drug can be in the blood before the injury begins.
The animal work was consistent. In mice with surgically induced sepsis, AP214 reduced kidney injury and improved survival, with the odd feature that middling doses worked better than high ones. In pigs, it kept kidney function far closer to normal after two hours of complete loss of blood flow to the only remaining kidney, and it blunted the lung pressure rise and heart weakening that bacterial endotoxin causes. In mouse inflammation models it worked through the MC3 receptor and also made macrophages better at clearing debris and dying cells.
People received it in a series of trials around heart surgery. The first, in the United States, closed early because patients enrolled too slowly; a second measured blood levels in 42 Danish patients; a third, in 77 Danish patients, reported less kidney injury in one of its two dose groups, the amount that later became the phase 2b trial's lowest arm; that result was presented only as a 2013 meeting abstract. AbbVie then took the drug, renamed ABT-719, into a 240-patient phase 2b trial at higher doses. Kidney injury rates were 63 to 70 percent in the three drug groups and 66 percent on placebo, with no change in kidney damage markers or 90-day outcomes. A companion trial in other major surgery was stopped in May 2014 for lack of efficacy, and no later trial has been registered.
Modimelanotide is one of several alpha-MSH analogues, and the only one aimed at the kidney. Afamelanotide, setmelanotide and bremelanotide reached approval for light sensitivity, rare genetic obesity and low sexual desire, each by targeting a different melanocortin receptor. Those drugs have their own entries and their own trials; nothing about them carries over to this one.
Mechanism of Action
Modimelanotide acts at the melanocortin receptors that alpha-MSH uses, chiefly MC3 on macrophages in the studies read, and turns down the inflammatory surge that follows a loss and return of blood flow.
Binds melanocortin receptors
The phase 2b paper describes it as binding MC1, MC3, MC4 and MC5, and ChEMBL records it as an MC1 and MC3 agonist. In mouse peritonitis its anti-inflammatory effect needed MC3 and did not need MC1 (PMIDs 27543797, 21703408).
Helps clear dying cells
Through MC3 it made macrophages take up more apoptotic neutrophils and particles, part of the process that ends inflammation rather than only preventing it (PMIDs 21703408, 22566831).
Protects the kidney in animals
In pigs with two hours of warm ischaemia and in septic mice, kidney function fell less and recovered sooner; the same approach did not lower kidney injury in heart-surgery patients (PMIDs 20172543, 18354376, 27543797).
Published Research
The studies below were read from their PubMed abstracts in November 2026: the one published human trial, four animal studies in mice and pigs, and two reviews. The trial paper's full text was also read for its dosing schedule and its account of the earlier Danish trial, whose results were never published as a paper. Two reviews title themselves for melanocortin receptors or for kidney injury rather than the drug, so their cards carry a sweep record quoting the words in the abstract that name it. Studies of alpha-MSH itself are listed under References, because they tested a different molecule. Older papers on ABT-719 as an antibiotic are about an unrelated Abbott compound that shared the code and are not cited here.
Phase 2b in high-risk heart surgery: no effect on kidney injury
Adults with stable kidney function having high-risk on-pump cardiac surgery in the United States and Denmark were randomised, double-blind, to placebo (61) or a total of 800 (59), 1,600 (61) or 2,100 (59) micrograms per kilogram. Acute kidney injury by AKIN creatinine and urine-output criteria within 48 hours developed in 65.5%, 62.7% and 69.6% of the three drug groups and 65.5% of the placebo group, with no pairwise difference. Newer injury biomarkers, intensive care stay and 90-day outcomes did not differ, and adverse events were about as common in every group.
Sepsis in mice: less kidney injury and better survival
Mice were given lethal or sublethal sepsis by tying and puncturing the caecum. AP214 reduced the resulting kidney injury along a bell-shaped curve, with the best effect at a middle dose, and it still helped when started six hours after the surgery. It raised the low blood pressure and slow heart rate of the lethal model, lowered blood TNF-alpha and IL-10, and reduced NF-kappaB activation in kidney and spleen and the death of spleen immune cells. Survival improved in both models.
Pig kidney after two hours without blood flow
In a blinded, randomised, placebo-controlled study of 26 pigs, surgeons removed the left kidney by laparoscopy and clamped the right kidney's blood supply for 120 minutes. AP214, 200 micrograms per kilogram intravenously on the day of surgery and for five days after, held mean peak creatinine to 3.92 mg/dL against 10.2 on placebo, and the lowest estimated filtration rate to 62.6 against 22.9 mL per minute per kilogram. Function bottomed out at 24 rather than 72 hours, and filtration on day 9 stayed higher (156 against 118).
Endotoxin shock in pigs: lung pressure and heart pumping
Anaesthetised young pigs received an infusion of bacterial endotoxin to cause a whole-body inflammatory response, with AP214 or saline as a single injection at the start. The drug cut the early spike in lung artery pressure and lung vascular resistance by about a third and stopped the fall in left ventricular fractional shortening seen on echocardiography in the controls, at both a low and a high dose.
Mouse inflammation: works through MC3 and speeds clean-up
In zymosan peritonitis, 400 to 800 micrograms per kilogram reduced the influx of white cells into the abdomen; the effect survived in mice with a broken MC1 receptor and disappeared in mice lacking MC3. In stimulated macrophages it cut IL-1beta release by about 80% and TNF-alpha and IL-6 by smaller amounts, and it made macrophages engulf more zymosan particles and apoptotic human neutrophils, again only when MC3 was present. It also lowered clinical scores in a mouse arthritis model.
Review: melanocortin receptors on macrophages
A review of how ACTH, alpha-MSH and synthetic agonists act on MC1 and MC3 receptors on macrophages to lower inflammatory cytokines and leukocyte recruitment. It singles out AP214's action at MC3 as the first evidence that a melanocortin drug can help macrophages clear particles and dead neutrophils, placing it among agents that promote the resolution of inflammation rather than only blocking its start.
Review: kidney injury drugs in trials
A review of drugs then in clinical trials for acute kidney injury, written with critically ill children in mind, where it affects more than a quarter of patients. It groups ABT-719 with recombinant alkaline phosphatase and AB103 as anti-inflammatory approaches, alongside antioxidants, vasodilators, apoptosis blockers and repair agents.
Dosing Data
Every amount below was given in AbbVie's phase 2b trial, by hospital staff, as 10-minute intravenous infusions timed to the stages of heart surgery. None of the three regimens lowered kidney injury compared with placebo, and the drug was never approved.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or 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 regulator's label that says in what form Modimelanotide is supplied. It is prepared and given by clinical staff, not bought and mixed at home: the next part says where.
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: Modimelanotide is prepared and given by clinical staff, in the operating room and intensive care unit, around heart surgery.
In the carded phase 2b trial it was given by hospital staff as timed intravenous infusions before incision, at aortic clamp release and in the hours after cardiac surgery.
Source: PMID 27543797 (a study carded under Research below).
Storage before and after mixing
Unknown: no label on file says how Modimelanotide is stored. It is kept and prepared by the hospital or clinic that gives it (see the part above); the home rules for a mixed vial in the mixing guide do not apply to it.
How it is taken
As it was given in human studies: Intravenous infusion over 10 minutes (Before incision, at aortic clamp release, 6 hours later; Study: phase 2b, lowest dose arm).
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of not reported in the sources read. After about five half-lives almost none is left.
How long the doses were given: Study: phase 2b, lowest dose arm: About 6 hours after clamp release; Study: phase 2b, middle dose arm: 24 hours after clamp release; Study: phase 2b, highest dose arm: 48 hours after clamp release.
When effects appear: unknown; no source on this page gives a time to effect for Modimelanotide. Results reported in the studies are under Published Research.
Source: half-life: PMID 27543797; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Adverse events occurred at similar rates on all three doses and on placebo in the 240-patient phase 2b trial (PMID 27543797); No difference from placebo in intensive care stay or in the trial's 90-day outcomes (PMID 27543797); Serious adverse events were recorded in 44% of the placebo group and in 21%, 22% and 48% of the lowest, middle and highest dose groups, and major cardiac events through 120 days in 5% to 7% of the first three groups and 12.5% of the highest dose group; the paper calls the safety profile broadly similar across groups (PMID 27543797, full text); AbbVie's second phase 2b trial was stopped for lack of efficacy, with the registry stating there were no safety concerns (NCT01897519); None of the papers read reports skin darkening, nausea or other effects known from melanocortin drugs; no study read was designed to look for them. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Modimelanotide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials above”).
Interactions
Unknown: a PubMed search for human interaction studies of Modimelanotide (reviewed 2026-11-04) 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 Modimelanotide 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: Discontinued (Never approved). Sport: Prohibited (S0 catch-all).
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
From the trials above. The patients were having major heart surgery, so most adverse events came from the operation and recovery, not necessarily from the drug.
Contraindications & Cautions
There is no label, so there are no official contraindications. These cautions follow from what the studies show.
Legal Status
An investigational drug whose development stopped in 2014. It was never approved or marketed anywhere.
Frequently Asked Questions
?What is modimelanotide?
A synthetic copy of the hormone alpha-MSH with six extra lysines at one end. It was developed as AP214 by Action Pharma and as ABT-719 by AbbVie to protect the kidneys of patients having heart surgery.
?Is it the same as Melanotan or afamelanotide?
No. All of them are built on alpha-MSH, but they are different molecules. Afamelanotide is approved for a light-sensitivity disorder and the Melanotan compounds are tanning peptides; modimelanotide was tested only for kidney protection, and none of its papers studied its effect on skin.
?Did it work?
Not in the trial that mattered. In 240 heart-surgery patients, kidney injury was as common on each of three doses as on placebo. An earlier Danish trial of 77 patients had reported less injury in one dose group, but that result, presented only as a meeting abstract, did not hold up.
?Why heart surgery?
Operations on a bypass pump reliably injure the kidneys in a large share of patients, the injury starts at a known time, and the drug can be given before it begins. That made it a clean test of whether an anti-inflammatory melanocortin drug protects people's kidneys the way it protected pigs' and mice's.
?Why do some ABT-719 papers talk about antibiotics?
Abbott used the same code in the 1990s for an unrelated antibacterial drug that blocks bacterial DNA gyrase. Those papers have nothing to do with modimelanotide.
?Can I buy it?
No. It was never approved or marketed and was only supplied to hospitals running its trials, as an intravenous infusion given around surgery. Development stopped in 2014.
References
- [clinical-trial] McCullough PA, et al. "ABT-719 for the Prevention of Acute Kidney Injury in Patients Undergoing High-Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial." J Am Heart Assoc, 2016;5(8). PMID: 27543797.
- [pubmed] Doi K, et al. "AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality." Kidney Int, 2008;73(11):1266-74. PMID: 18354376.
- [pubmed] Simmons MN, et al. "Alpha-melanocyte stimulating hormone analogue AP214 protects against ischemia induced acute kidney injury in a porcine surgical model." J Urol, 2010;183(4):1625-9. PMID: 20172543.
- [pubmed] Kristensen J, et al. "The α-MSH analogue AP214 attenuates rise in pulmonary pressure and fall in ejection fraction in lipopolysaccharide-induced systemic inflammatory response syndrome in pigs." Clin Physiol Funct Imaging, 2011;31(1):54-60. PMID: 21029328.
- [pubmed] Montero-Melendez T, et al. "The melanocortin agonist AP214 exerts anti-inflammatory and proresolving properties." Am J Pathol, 2011;179(1):259-69. PMID: 21703408.
- [review] Patel HB, et al. "Melanocortin receptors as novel effectors of macrophage responses in inflammation." Front Immunol, 2011;2:41. PMID: 22566831.
- [review] Benoit SW, et al. "Acute kidney injury: emerging pharmacotherapies in current clinical trials." Pediatr Nephrol, 2018;33(5):779-787. PMID: 28601936.
- [pubmed] Chiao H, et al. "Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats." J Clin Invest, 1997;99(6):1165-72. PMID: 9077523.
- [pubmed] van Rijt WG, et al. "α-Melanocyte stimulating hormone treatment in pigs does not improve early graft function in kidney transplants from brain dead donors." PLoS One, 2014;9(4):e94609. PMID: 24728087.
- [pubmed] Gallagher KM, et al. "Recent early clinical drug development for acute kidney injury." Expert Opin Investig Drugs, 2017;26(2):141-154. PMID: 27997816.
- [registry] ClinicalTrials.gov API v2, read November 4, 2026: Action Pharma A/S sponsored NCT00628264 (phase 2, three 10-minute AP214 infusions in cardiac surgery, United States, terminated because recruitment was much slower than planned), NCT00903604 (phase 2 pharmacokinetics, three ascending-dose infusions, 42 patients, Denmark, completed June 2010) and NCT01256372 (exploratory phase 2, two dosing regimens against placebo, 77 patients, Denmark, completed August 2011, no results posted). AbbVie sponsored NCT01777165 (phase 2b, 240 patients in the United States and Denmark, completed March 2014) and NCT01897519 (phase 2b in high-risk major cardiothoracic or vascular surgery, 56 enrolled, terminated May 2014: 'Topline results from study M13-796 showed an overall lack of efficacy. There were no safety concerns.'). https://clinicaltrials.gov/study/NCT01897519
- [other] ChEMBL CHEMBL3545104 (modimelanotide), read November 4, 2026: synonyms ABT-719, AP214, AP-214, ZP1480, ZP-1480 and modimelanotida; maximum phase 2; mechanisms recorded as melanocortin receptor 1 agonist and melanocortin receptor 3 agonist. https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL3545104/
- [other] European Medicines Agency, medicines and orphan designation data exports (JSON), read November 4, 2026: no record for modimelanotide, ABT-719 or AP214 among 2,754 medicines or 3,310 orphan designations. https://www.ema.europa.eu/en/medicines/download-medicine-data
- [other] US FDA, Drugs@FDA (openFDA drugsfda endpoint), searched November 4, 2026: no application for modimelanotide, ABT-719 or AP214.
Sources & Citations
Every study on this page was read from its PubMed record on November 4, 2026, and the phase 2b trial's full text from PubMed Central the same day. Trial registrations come from ClinicalTrials.gov, the codes and receptor targets from ChEMBL, and regulatory status from Drugs@FDA and the European Medicines Agency's data exports, read the same day. 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.