Apelin-13
Also known as: [Pyr1]-Apelin-13 · APJ Ligand
Apelin-13 is the shortest and most potent naturally occurring fragment of the apelin peptide family, the endogenous ligand for the APJ receptor. The predominant circulating and cardiac form, [Pyr1]-Apelin-13, has been directly tested in real human infusion studies showing increased cardiac output and reduced vascular resistance in both healthy volunteers and heart failure patients. No formulation has FDA approval, and its very short plasma half-life has driven pharmaceutical interest toward longer-acting synthetic analogs and small-molecule APJ agonists rather than the native peptide itself. Research-grade material sold here is a separate product intended solely for laboratory research.
What is Apelin-13?
Apelin-13 is the shortest and most biologically potent naturally occurring processed fragment of the apelin peptide family, all derived from a common 77-amino-acid precursor (preproapelin) and including longer fragments such as apelin-17 and apelin-36. Apelin-13 is the endogenous ligand for the APJ receptor (also called the apelin receptor, APLNR), a G protein-coupled receptor structurally related to the angiotensin AT1 receptor but activated by an entirely distinct peptide.
At Verified Peptides, we want to clarify an important structural detail: the predominant form of Apelin-13 found in human plasma and cardiac tissue carries a post-translationally modified N-terminal pyroglutamate residue in place of the original glutamine, denoted [Pyr1]-Apelin-13 (sequence XRPRLSHKGPMPF, where X is pyroglutamate). This pyroglutamyl modification confers greater resistance to enzymatic degradation than the unmodified glutamine-containing form and is the specific form used in essentially all the human clinical research described in this profile, as well as the form most commonly sold under the name "Apelin-13" by research suppliers.
Chemically, [Pyr1]-Apelin-13 has molecular formula C69H108N22O16S, an approximate molecular weight of 1,533.8 g/mol (calculated from the formula), CAS number 217082-60-5, and PubChem CID 25085173. It binds the APJ receptor with high affinity (reported dissociation constant around 4.5 nM for the human receptor) and is described in pharmacological literature as a highly potent agonist (EC50 approximately 0.37 nM in functional assays).
The apelin peptide family's precursor, preproapelin, undergoes proteolytic processing to generate several bioactive fragments of different lengths — apelin-36, apelin-17, and apelin-13 among them — all of which retain the same C-terminal region responsible for APJ receptor binding, but differ in their N-terminal extensions, plasma stability, and relative tissue distribution. Apelin-13, as the shortest processed fragment, is generally reported as the most potent of these fragments at the APJ receptor, which is part of why it has been the primary focus of both mechanistic and clinical research within the broader apelin family, rather than the longer apelin-17 or apelin-36 forms.
Key Benefits & Mechanisms
Mechanism of action
Apelin-13 activates the APJ receptor, triggering Gi/Go-protein-coupled signaling that produces several distinct cardiovascular effects: direct positive inotropic (contractility-enhancing) action on cardiac muscle, vasodilation of both arteries and veins via nitric-oxide-dependent and nitric-oxide-independent pathways, and a diuretic/natriuretic effect on the kidney. The apelin/APJ system is now understood to function, in some respects, as a counter-regulatory system to the classical renin-angiotensin system, with effects that in several contexts oppose those of Angiotensin II, similar in broad concept (though mechanistically distinct) to how Angiotensin (1-7), also built on this site, opposes classical RAS signaling through the separate Mas receptor.
Apelin-13's plasma stability is notably poor — the peptide is rapidly degraded by circulating peptidases, with a very short functional half-life. This pharmacokinetic limitation is central to understanding its research and clinical development history: rather than being suitable for infrequent bolus dosing, meaningful pharmacological effects require continuous or repeated infusion, a limitation that has directly motivated pharmaceutical efforts toward longer-acting cyclic peptide analogs (such as CLR325, a synthetic apelin-13 analog in clinical development) and unrelated small-molecule APJ receptor agonists (such as BMS-986224), designed specifically to overcome apelin-13's short duration of action while retaining APJ receptor activation.
The clearest human evidence for this mechanism comes from a real clinical infusion study (Japp et al., Circulation, 2010, PMID 20385929), in which systemic infusions of [Pyr1]-Apelin-13 (30 to 300 nmol/min) in both healthy volunteers and chronic heart failure patients increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance — direct, in vivo human confirmation of the peptide's predicted cardiovascular pharmacology.
The apelin/APJ system's positive inotropic effect is mechanistically distinct from that of classical inotropic agents such as digoxin or dobutamine, which act through entirely different pathways (sodium-potassium ATPase inhibition and beta-adrenergic receptor stimulation, respectively). This distinct mechanism is part of what generated research and pharmaceutical interest in the apelin/APJ pathway as a potentially novel therapeutic route for improving cardiac contractility in heart failure without relying on the same adrenergic or ion-pump mechanisms already targeted by existing heart failure therapies, some of which carry their own well-documented long-term risks with chronic use.
Research Summary
At Verified Peptides, we think Apelin-13's evidence base is genuinely substantial for a peptide that has not reached drug approval, anchored by real human clinical data rather than only preclinical or single-institute research. The pivotal human study (PMID 20385929) directly infused [Pyr1]-Apelin-13 into human subjects — both healthy volunteers and patients with chronic heart failure already receiving standard optimal pharmacological treatment (ACE inhibitors and/or beta-blockers) — and found that apelin's beneficial hemodynamic effects (increased cardiac index, reduced vascular resistance) were preserved even on top of this existing standard therapy, suggesting an additive rather than redundant mechanism relative to conventional heart failure treatment.
A separate line of research has examined apelin-13's role in end-stage heart failure directly in explanted human cardiac tissue (PMID 22082814), reporting cardioprotective effects on cardiac performance and remodeling measures, complementing the human infusion data with tissue-level mechanistic findings. Additional research has documented that myocardial apelin and APJ receptor expression are themselves upregulated in ischemic heart failure, suggesting the endogenous apelin system may represent a natural, if insufficient, compensatory response to cardiac injury that exogenous apelin-13 administration is designed to reinforce.
We want to be clear about where apelin-13's development currently stands: despite this real, encouraging human physiological data, no apelin-13-based therapy has reached FDA approval, and the field has substantially shifted toward longer-acting synthetic analogs (CLR325) and structurally unrelated small-molecule APJ agonists specifically because native apelin-13's poor plasma stability makes it impractical as a standalone drug requiring only occasional dosing. This is an honest and important distinction: the human proof-of-concept data support the APJ receptor as a legitimate therapeutic target, but native apelin-13 itself is better understood as a validated research tool and mechanistic reference compound than as a viable standalone drug candidate given its pharmacokinetic limitations.
No apelin-13 formulation has received FDA approval. At Verified Peptides, we sell research-grade Apelin-13 exclusively for laboratory research, and we think its combination of genuine human infusion data, tissue-level cardioprotective findings, and a clear, honestly-documented pharmacokinetic limitation driving the field toward alternative APJ-targeting molecules makes it a well-characterized and instructive research compound.
Common Stacks
Lesser-Known Facts About Apelin-13
The apelin/APJ system has drawn substantial research interest in metabolic disease contexts beyond cardiovascular hemodynamics: apelin is also produced by adipose tissue (fat cells), and its expression and circulating levels are altered in obesity and insulin resistance, making the apelin/APJ axis a subject of research interest in metabolic syndrome and type 2 diabetes, a distinct research thread from its cardiovascular applications.
The APJ receptor has an unusual dual role relevant to a completely separate field: it was independently identified as a co-receptor that certain strains of HIV can use, alongside CD4 and CCR5/CXCR4, to enter host cells — a finding from HIV entry research that predates and is mechanistically unrelated to APJ's cardiovascular apelin-receptor biology, illustrating how a single receptor can have entirely separate research histories in different fields.
A specific metabolite of [Pyr1]-Apelin-13, called [Pyr1]Apelin-13(1-12) — generated by ACE2 (the same enzyme that generates Angiotensin (1-7) from Angiotensin II, also built on this site) cleaving one residue from the parent peptide — has been shown to retain biological activity as a distinct APJ-active fragment, adding another point of mechanistic overlap between the apelin and angiotensin systems beyond their both being described as RAS counter-regulatory peptides.
Separately from its cardiovascular research applications, intravenously administered [Pyr1]-Apelin-13 has been studied in mouse models of inflammatory pain, reportedly acting through the kappa opioid receptor system — a mechanistically distinct and less-established research direction compared to the cardiovascular literature, illustrating the apelin system's surprisingly broad range of investigated biological roles.
Purity & Sourcing Considerations
At Verified Peptides, we require independent third-party HPLC purity testing and mass spectrometry identity confirmation for every batch of research-grade Apelin-13 we offer, with a Certificate of Analysis (COA) available for each lot. As a 13-residue peptide with a specific pyroglutamate N-terminal modification ([Pyr1]-Apelin-13), researchers should confirm that the specific form they receive matches this predominant, pyroglutamyl-modified sequence used in the cited human research, rather than the less common unmodified glutamine-containing variant.
We source exclusively from manufacturers operating under Good Manufacturing Practice (GMP)-aligned quality systems, and every lot is independently verified rather than accepted solely on a supplier's internal documentation. Researchers should always request and review the specific COA for the lot they receive, confirming purity percentage and molecular identity before use in any experimental protocol.
Storage & Stability
Lyophilized Apelin-13 is stable when stored at -20°C, protected from light and moisture, and researchers can generally expect the unreconstituted peptide to maintain integrity over an extended period under these conditions. At Verified Peptides, we ship lyophilized peptide with appropriate cold-chain packaging to preserve stability in transit.
Once reconstituted, Apelin-13 solution should be stored refrigerated at 2–8°C and used promptly, given the compound's well-documented poor plasma stability and general susceptibility to peptidase-mediated degradation — the same pharmacokinetic limitation that drove pharmaceutical development toward longer-acting analogs is also relevant to in vitro handling and experimental design, since degraded peptide will not produce the same activity as intact material.
Researchers should avoid repeated freeze-thaw cycles of reconstituted material and should follow the specific storage guidance provided with each lot's documentation, with particular attention to using freshly reconstituted material promptly given this peptide's inherent instability.
Frequently asked questions about Apelin-13
What is Apelin-13 and what does it do?
Apelin-13 is the shortest, most potent naturally occurring fragment of the apelin peptide family, the endogenous ligand for the APJ receptor. It produces cardiac contractility enhancement, vasodilation, and diuretic effects, and is studied primarily in cardiovascular and heart failure research.
Is there human clinical data for Apelin-13?
Yes. A real clinical infusion study (PMID 20385929, Circulation 2010) administered [Pyr1]-Apelin-13 intravenously to both healthy volunteers and chronic heart failure patients, finding increased cardiac index and reduced vascular resistance, with effects preserved even in patients already on standard heart failure medications.
Why hasn't Apelin-13 become an approved drug despite positive human data?
Apelin-13 has very poor plasma stability and a very short functional half-life, requiring continuous infusion rather than practical periodic dosing. This limitation has driven pharmaceutical development toward longer-acting synthetic analogs (such as CLR325) and unrelated small-molecule APJ receptor agonists rather than native apelin-13 itself.
What is the difference between Apelin-13 and [Pyr1]-Apelin-13?
Apelin-13 has an N-terminal glutamine residue in its unmodified form. [Pyr1]-Apelin-13 has this glutamine post-translationally converted to pyroglutamate, which confers greater resistance to enzymatic degradation. [Pyr1]-Apelin-13 is the predominant form found in human plasma and myocardium and the form used in essentially all cited human research.
How does Apelin-13 relate to the renin-angiotensin system?
Apelin-13 and Angiotensin(1-7) are both considered counter-regulatory to the classical renin-angiotensin system's pathological effects, though they act through entirely separate receptors (APJ versus Mas). A specific apelin-13 metabolite is also generated by ACE2, the same enzyme responsible for producing Angiotensin(1-7), adding a point of mechanistic overlap.
Does Apelin-13 have any research relevance outside cardiovascular disease?
Yes. The apelin/APJ system is also studied in metabolic disease contexts (apelin is produced by adipose tissue and altered in obesity/insulin resistance), and the APJ receptor has a separate, mechanistically unrelated research history as an HIV co-receptor. Apelin-13 has also been studied in mouse inflammatory pain models via the kappa opioid receptor.
Is Apelin-13 FDA approved?
No. Despite genuine positive human infusion data, no apelin-13-based formulation has received FDA approval. Development interest has shifted toward longer-acting analogs and small-molecule APJ agonists designed to overcome native apelin-13's pharmacokinetic limitations.
What administration route was used in Apelin-13 human research?
The pivotal human study used continuous intravenous infusion, reflecting the peptide's requirement for sustained delivery given its short plasma half-life. This describes methodology used in published clinical research, not usage instructions — Verified Peptides does not provide dosing guidance for human or animal administration.
How does Apelin-13 compare to apelin-17 and apelin-36?
All three are processed fragments of the same preproapelin precursor, sharing the C-terminal region responsible for APJ receptor binding but differing in N-terminal length, plasma stability, and tissue distribution. Apelin-13, the shortest fragment, is generally reported as the most potent at the APJ receptor, which is why it has been the primary focus of cardiovascular mechanistic and clinical research within the apelin family.
Legal & research status: Apelin-13 has not been approved by the FDA, EMA, or any other regulatory body for any indication. Material sold as a research peptide is offered strictly for laboratory and research use, not for human consumption or therapeutic use.