Cenderitide
A Mayo Clinic designer peptide that activates both natriuretic peptide receptors
Cenderitide, first called CD-NP, joins human C-type natriuretic peptide (CNP) to the 15-amino-acid tail of a natriuretic peptide from green mamba venom (DNP). The fusion was built so that one molecule switches on both natriuretic peptide receptors, GC-A and GC-B, for kidney and anti-scarring effects without a large fall in blood pressure. Two small human studies, in healthy volunteers and in stable heart failure, found it raised the messenger molecule cGMP and was well tolerated. It is not approved anywhere.
No established human dose Details ↓
Recommended Dosing
No established human dose
Cenderitide has been given to people in two small studies, a first study in healthy volunteers and a four-hour intravenous infusion in stable chronic heart failure. Neither abstract states the amount infused, and no later trial has published one, so there is no human dose to show here.
What is it?
The body makes three natriuretic peptides. ANP and BNP come mainly from the heart and act through the receptor GC-A; they make the kidneys shed salt and water and they lower blood pressure. CNP acts through a second receptor, GC-B. It relaxes veins, slows the growth of the heart's scar-forming fibroblasts and lowers blood pressure less than the heart peptides, but it has little effect on the kidneys. Cenderitide is an attempt to get the useful parts of both in one molecule. Mayo Clinic researchers took the 22 amino acids of human CNP and attached the 15-amino-acid tail of DNP, a natriuretic peptide from the venom of the green mamba, and reported the design in 2008 under the name CD-NP.
Laboratory work explains why the tail matters. In human kidney cells engineered to carry one receptor or the other, cenderitide strongly activated both, while plain CNP and three CNP-based variants without the DNP tail were weak at one of them. The long tail also made the peptide harder to break down: in human kidney membranes it lasted about 13 times longer than ANP, 3 times longer than BNP and 4 times longer than CNP, and the authors group it with the long-tailed peptides that resist neprilysin, the enzyme that clears CNP. In animals it increased urine flow, salt excretion and the kidneys' filtering rate, inhibited renin, and lowered blood pressure less than BNP. Given under the skin for two weeks to rats with one kidney removed, it limited scarring of the heart's main pumping chamber while preserving its function.
Two small human studies followed, both from the same Mayo group. In healthy volunteers, the first study found that cenderitide raised cGMP, increased salt excretion and lowered aldosterone without an excessive fall in blood pressure. In people with stable chronic heart failure, a study listed on PubMed as randomised and double-blind gave a four-hour intravenous infusion and found it safe and well tolerated, with higher cGMP in blood and urine and no change in blood pressure. No larger or longer trial has been published.
Other work tested delivery and new uses. Researchers built slow-release gels, films and drug-coated stents that release the peptide over days to weeks; a coated stent in pigs improved the lining's healing over the struts but did not reduce re-narrowing compared with a bare metal stent. In mice, ten days of treatment turned some white fat into a heat-burning type, but twelve weeks on a high-fat diet led to more weight gain, worse glucose tolerance and fatty liver, so longer use raised questions the authors flag themselves. No study gives a human dose in its abstract, and none of the abstracts read reports a half-life in people.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Published Research
Studies of cenderitide (CD-NP), from their PubMed abstracts. Two are human studies; the rest are dog, rat, mouse, pig and cell work and reviews, many from the Mayo Clinic group that designed it. This entry is mid tier because only two small, short human studies exist.
First study in healthy volunteers
The first test in people showed that CD-NP raised cGMP, increased sodium excretion and suppressed aldosterone in healthy volunteers without an excessive drop in blood pressure. The abstract does not give the number of volunteers or the amounts infused.
Stable chronic heart failure
In the first clinical trial in heart failure (indexed on PubMed as randomised and double-blind), a four-hour intravenous infusion of cenderitide was safe and well tolerated. Plasma cGMP and urinary cGMP excretion rose, blood pressure did not change, and no adverse effects were reported. The abstract does not state the dose or the number of patients.
The design and first animal tests
The paper describing the fusion of CNP with DNP's tail reports that, in animals, CD-NP increased urine and salt output and the kidneys' filtration rate, eased the load on the heart and inhibited renin, and lowered blood pressure less than BNP. In heart fibroblasts it raised cGMP and slowed their growth.
Why the DNP tail matters, in dogs
Only cenderitide, and not CNP or three CNP-based variants, strongly activated both receptors in engineered human kidney cells. In normal dogs it raised urinary and kidney cGMP, salt excretion and filtration rate (from about 37 to 51 mL per minute), where CNP did not, and it raised cGMP in isolated glomeruli eight times more than CNP.
Heart scarring in rats
In rats with early heart fibrosis after removal of one kidney, two weeks of CD-NP under the skin reduced fibrosis in the left ventricle and lowered aldosterone while preserving systolic and diastolic function, compared with rats given an inactive vehicle. In cells it produced cGMP through both GC-A and GC-B.
Fat tissue and metabolism in mice
In mouse fat cells CD-NP raised cGMP and thermogenic markers, and ten days of treatment browned white fat. Over twelve weeks in diet-induced obese mice it reduced fat inflammation but increased body mass, worsened glucose tolerance and caused fatty liver, with more of the clearance receptor NPR-C and less fat breakdown.
A slow-release gel in rats
A gel injected under the skin of rats kept CD-NP levels raised in plasma for three weeks. Plasma cGMP unexpectedly drifted down over that time while urinary cGMP stayed high, which the authors read as the body compensating for high exposure.
Cenderitide-coated stents in pigs
Sixteen pigs received 32 stents. Coated stents released the peptide and showed more endothelial coverage over and between struts, with mild inflammation, but neither plasma cGMP nor re-narrowing differed from bare metal stents at 28 days.
Resistance to breakdown
In human kidney membranes, CD-NP was inactivated about 13, 3 and 4 times more slowly than ANP, BNP and CNP. Both a neprilysin inhibitor and the broad protease inhibitor leupeptin blocked its breakdown; the authors group it with BNP and DNP as long-tailed peptides cleared mainly by leupeptin-sensitive proteases, and credit this stability for part of its effect.
Stent coating and vessel cells
Released from coated films and stents for up to seven days, CD-NP slowed the growth of human coronary artery smooth muscle cells without slowing human endothelial cells, the selectivity wanted in a stent drug.
A peptide-releasing film for the heart
Biodegradable films released cenderitide for 30 days. The released peptide kept its activity, raising cGMP and holding back growth and DNA synthesis in enlarged human cardiac fibroblasts, as well as or better than daily dosing in the dish.
Controlled-release matrices
Polymer matrices loaded with CD-NP either released too much at once or too little; adding polyethylene glycol or its copolymer evened out release, and the released peptide still raised cGMP and inhibited human cardiac fibroblasts.
Rationale and early data
A review of CD-NP as a dual GC-A and GC-B activator that combines CNP's anti-scarring effects with DNP's salt-shedding and aldosterone-lowering effects, and preserves kidney filtration with little blood-pressure lowering compared with nesiritide.
The developers' overview
The Mayo group reviews natriuretic peptide biology, the design of cenderitide as a first-in-class dual receptor activator for heart failure, and the clinical studies that followed.
Side Effects & Contraindications
Reported Side Effects
Human safety data come from two small studies of short infusions.
Contraindications & Cautions
There is no label.
Legal Status
We found no approval for cenderitide anywhere.
Frequently Asked Questions
?What is cenderitide?
A designer peptide made at the Mayo Clinic by joining human C-type natriuretic peptide to the tail of a natriuretic peptide from green mamba venom. It was first called CD-NP.
?What was it designed to do?
Activate both natriuretic peptide receptors, GC-A and GC-B, so that it helps the kidneys and limits heart scarring without dropping blood pressure as much as nesiritide does.
?Has it been tested in people?
In two small studies: a first-in-human study in healthy volunteers (2009) and a randomised, double-blind study of a four-hour infusion in stable heart failure (2018). Both found it raised cGMP and was well tolerated. No larger trial has been published.
?Is there a dose?
No dose is shown here. Neither human abstract states the amount infused, so any figure would be a guess.
?How does it differ from nesiritide and CNP?
Nesiritide is BNP and acts on GC-A, lowering blood pressure strongly. CNP acts on GC-B and has little kidney effect. Cenderitide acts on both and, in animals, lowered blood pressure less than BNP while improving kidney filtration.
References
- [clinical-trial] Lee CY, et al. "Pharmacodynamics of a novel designer natriuretic peptide, CD-NP, in a first-in-human clinical trial in healthy subjects." J Clin Pharmacol, 2009;49(6):668-73. PMID: 19395584.
- [clinical-trial] Kawakami R, et al. "A Human Study to Evaluate Safety, Tolerability, and Cyclic GMP Activating Properties of Cenderitide in Subjects With Stable Chronic Heart Failure." Clin Pharmacol Ther, 2018;104(3):546-552. PMID: 29226471.
- [pubmed] Lisy O, et al. "Design, synthesis, and actions of a novel chimeric natriuretic peptide: CD-NP." J Am Coll Cardiol, 2008;52(1):60-8. PMID: 18582636.
- [pubmed] Lee CY, et al. "Cenderitide: structural requirements for the creation of a novel dual particulate guanylyl cyclase receptor agonist with renal-enhancing in vivo and ex vivo actions." Eur Heart J Cardiovasc Pharmacother, 2016;2(2):98-105. PMID: 27340557.
- [pubmed] Martin FL, et al. "CD-NP: a novel engineered dual guanylyl cyclase activator with anti-fibrotic actions in the heart." PLoS One, 2012;7(12):e52422. PMID: 23272242.
- [pubmed] Glöde A, et al. "Divergent effects of a designer natriuretic peptide CD-NP in the regulation of adipose tissue and metabolism." Mol Metab, 2017;6(3):276-287. PMID: 28271034.
- [pubmed] Lim SG, et al. "In-vivo evaluation of an in situ polymer precipitation delivery system for a novel natriuretic peptide." PLoS One, 2013;8(2):e52484. PMID: 23441143.
- [pubmed] Huang Y, et al. "In vivo Evaluation of Cenderitide-Eluting Stent (CES) II." Ann Biomed Eng, 2016;44(2):432-41. PMID: 26178873.
- [pubmed] Dickey DM, et al. "Dendroaspis natriuretic peptide and the designer natriuretic peptide, CD-NP, are resistant to proteolytic inactivation." J Mol Cell Cardiol, 2011;51(1):67-71. PMID: 21459096.
- [pubmed] Ng XW, et al. "In vitro evaluation of cenderitide-eluting stent I -an antirestenosis and proendothelization approach." J Pharm Sci, 2014;103(11):3631-3640. PMID: 25223419.
- [pubmed] Ng XW, et al. "Cenderitide-eluting film for potential cardiac patch applications." PLoS One, 2013;8(7):e68346. PMID: 23861890.
- [pubmed] Ng XW, et al. "Investigation of cenderitide controlled release platforms for potential local treatment of cardiovascular pathology." J Pharm Sci, 2014;103(5):1400-10. PMID: 24590596.
- [review] McKie PM, et al. "CD-NP: an innovative designer natriuretic peptide activator of particulate guanylyl cyclase receptors for cardiorenal disease." Curr Heart Fail Rep, 2010;7(3):93-9. PMID: 20582736.
- [review] Ichiki T, et al. "Natriuretic peptide based therapeutics for heart failure: Cenderitide: A novel first-in-class designer natriuretic peptide." Int J Cardiol, 2019;281:166-171. PMID: 29941213.
- [review] Wojta J. "Cenderitide: a multivalent designer-peptide-agonist of particulate guanylyl cyclase receptors with considerable therapeutic potential in cardiorenal disease states." Eur Heart J Cardiovasc Pharmacother, 2016;2(2):106-7. PMID: 27533521.
- [other] PubChem CID 155817506, Cenderitide: formula C158H264N48O51S3, molecular weight 3748.3. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/155817506
Sources & Citations
Studies were read from their PubMed records, October 29, 2026.
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. Consult a licensed healthcare provider before making health decisions.