Evidence map›Paper›PMID 27340557›Full record

ArticleEuropean heart journal. Cardiovascular pharmacotherapy2016

Cenderitide: structural requirements for the creation of a novel dual particulate guanylyl cyclase receptor agonist with renal-enhancing in vivo and ex vivo actions.

Candace Y W Lee, Brenda K Huntley, Daniel J McCormick, Tomoko Ichiki, S Jeson Sangaralingham, Ondrej Lisy, John C Burnett

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European heart journal. Cardiovascular pharmacotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 30 citations in OpenAlex.

  1. Trial
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  4. Cross talk on therapeutic strategies: natriuretic peptides and inhibiting neprilysin in hypertension management.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
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  6. Article
  7. Osteocrin, a bone-derived humoral factor, exerts a renoprotective role in ischemia-reperfusion injury in mice.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022
    Article
  8. Review
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  14. Article
  15. Innovative Therapeutics: Designer Natriuretic Peptides.JACC. Basic to translational science · 2016
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Candace Y W LeeCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Medicine, Bioengineering & Physiology, and Biochemistry and Molecular Biology, College of Medicine Mayo Clinic, Guggenheim 915, 200 First Street S.W., Rochester, MN 55905, USA.
Brenda K HuntleyCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Medicine, Bioengineering & Physiology, and Biochemistry and Molecular Biology, College of Medicine Mayo Clinic, Guggenheim 915, 200 First Street S.W., Rochester, MN 55905, USA.
Daniel J McCormickCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Medicine, Bioengineering & Physiology, and Biochemistry and Molecular Biology, College of Medicine Mayo Clinic, Guggenheim 915, 200 First Street S.W., Rochester, MN 55905, USA.
Tomoko IchikiCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Medicine, Bioengineering & Physiology, and Biochemistry and Molecular Biology, College of Medicine Mayo Clinic, Guggenheim 915, 200 First Street S.W., Rochester, MN 55905, USA.
S Jeson SangaralinghamCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Medicine, Bioengineering & Physiology, and Biochemistry and Molecular Biology, College of Medicine Mayo Clinic, Guggenheim 915, 200 First Street S.W., Rochester, MN 55905, USA.
Ondrej LisyCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Medicine, Bioengineering & Physiology, and Biochemistry and Molecular Biology, College of Medicine Mayo Clinic, Guggenheim 915, 200 First Street S.W., Rochester, MN 55905, USA.
John C BurnettCardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Medicine, Bioengineering & Physiology, and Biochemistry and Molecular Biology, College of Medicine Mayo Clinic, Guggenheim 915, 200 First Street S.W., Rochester, MN 55905, USA burnett.john@mayo.edu.
Mayo Clinic · US

Funding

Recruitment and Phenotyping CoreP01HL076611 · NHLBI · MAYO CLINIC ROCHESTER · PI BURNETT, JOHN C · 2005 to 2015
$19.6M
INTRARENAL REGULATION OF SODIUM EXCRETIONR01HL036634 · NHLBI · MAYO CLINIC ROCHESTER · PI BURNETT, JOHN C · 1987 to 2019
$6.5M
Cardiovascular Peptides and Myocardial InfarctionR01HL083231 · NHLBI · MAYO CLINIC ROCHESTER · PI BURNETT, JOHN C, CHEN, HORNG H · 2006 to 2016
$4.6M
NHLBI NIH HHS P01 HL076611NHLBI NIH HHS R01 HL036634NHLBI NIH HHS R01 HL083231
6 · The paper itself

Abstract

aimsCenderitide is a novel dual natriuretic peptide (NP) receptor chimeric peptide activator, which targets the particulate guanylyl cyclase B (pGC-B) receptor and pGC-A unlike native NPs. Cenderitide was engineered to retain the anti-fibrotic properties of C-type natriuretic peptide (CNP)/pGC-B with renal-enhancing actions facilitated by fusion to the carboxyl terminus of Dendroaspis NP (DNP), a pGC-A agonist, to CNP. Here, we address significance of the DNP carboxyl terminus in dual pGC receptor activation and actions of cenderitide compared with CNP on renal function and cyclic guanosine monophosphate (cGMP) in vivo and ex vivo in normal canines. METHODS AND

resultsIn vitro, only cenderitide and not CNP or three CNP-based variants was a potent dual pGC-A/pGC-B activator of cGMP production (from 5 to 237 pmol/mL) in human embryonic kidney (HEK) 293 cells overexpressing human pGC-A while in pGC-B overexpressing cells cenderitide increased cGMP production (from 4 to 321 pmol/mL) while the three CNP-based variants were weak agonists. Based upon our finding that the DNP carboxyl terminus is a key structural requirement for dual pGC-A/pGC-B activation, we defined in vivo the renal-enhancing actions of cenderitide compared with CNP. Cenderitide increased urinary cGMP excretion (from 989 to 5977 pmol/mL), net generation of renal cGMP (821-4124 pmol/min), natriuresis (12-242 μEq/min), and glomerular filtration rate (GFR) (37-51 mL/min) while CNP did not. We then demonstrated the transformation of CNP ex vivo into a renal cGMP-activating peptide which increased cGMP in freshly isolated glomeruli eight-fold greater than CNP.

conclusionThe current study establishes that dual pGC-A and pGC-B activation with CNP requires the specific carboxyl terminus of DNP. In normal canines in vivo and in glomeruli ex vivo, the carboxyl terminus of DNP transforms CNP into a natriuretic and GFR-enhancing peptide. Future studies of cenderitide are warranted in cardiorenal disease states to explore its efficacy in overall cardiorenal homeostasis.

Indexed as

AnimalsAtrial Natriuretic Factor Receptor BCyclic GMPDendroaspisDogsDrug DesignGlomerular Filtration RateHEK293 CellsHumansKidney Function TestsMaleNatriuretic AgentsNatriuretic Peptide, C-TypeNatriuretic PeptidesReceptors, Atrial Natriuretic FactorRenal AgentsAtrial Natriuretic Factor Receptor Batrial natriuretic factor receptor CcenderitideCyclic GMPNatriuretic AgentsNatriuretic Peptide, C-TypeNatriuretic PeptidesReceptors, Atrial Natriuretic FactorRenal AgentsSnake VenomscanineCD-NPChimeric natriuretic peptideC-type natriuretic peptide

Identifiers

PMID27340557
PMCPMC4853826
OpenAlexW2281781247

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.