CJC-1295 (no DAC) + Ipamorelin 5 mg / 5 mg

Compound profile

CJC-1295 / Ipamorelin: compound profile, literature landscape and handling notes

Where CJC-1295 / Ipamorelin came from

The GHRH side of this blend descends from a line of work that began when growth hormone-releasing hormone was isolated from pancreatic tumor tissue and shown to be a 44-residue peptide whose full activity survived truncation to its first 29 residues. That fragment, prepared as the C-terminal amide, became sermorelin, and it is the parent structure for everything in this part of the catalog that is described as a GHRH analog. Sermorelin is a faithful fragment, which is both its virtue as a reference compound and its weakness as a working reagent: it carries every liability of the native sequence, including a penultimate alanine that makes it a clean substrate for dipeptidyl peptidase-4.

The molecule in this vial is what you get when medicinal chemists take that fragment and repair its four most obvious weak points by substitution. That tetrasubstituted backbone was developed by ConjuChem as the peptide half of a longer-acting construct, and the name CJC-1295 properly belongs to the finished construct, which carried an additional C-terminal residue bearing a reactive linker known as the Drug Affinity Complex. The bare substituted peptide without that linker had no separate trade name, so the research-chemical market back-formed one, and it is now sold almost universally as CJC-1295 no-DAC. The precise name in the older chemistry literature is modified GRF(1-29). Both names appear on documentation, and knowing that they refer to the same substance saves a great deal of confusion.

Ipamorelin comes from an entirely separate program. It emerged from work in the 1990s on synthetic growth hormone secretagogues, a class that had begun with enkephalin-derived hexapeptides and had already produced GHRP-6 and hexarelin. Ipamorelin was reported as a pentapeptide designed for selectivity rather than raw efficacy, and the published claim that distinguished it was not that it released more growth hormone than its predecessors but that it did so with markedly less cross-activation of the corticotropic and lactotropic axes in the preclinical models used at the time. That selectivity claim is the entire reason the compound is still discussed, and it is worth reading the primary description rather than the secondary summaries of it.

Reading the structure of CJC-1295 / Ipamorelin

The sequence, formula and mass figures for both components are printed in the specification table further down this page. What is worth doing here is reading the substitutions, because the GHRH component of this blend is the clearest worked example in the whole catalog of rational stabilization by amino-acid replacement, and once you can read it you can read most of the others.

Four positions differ from the native GRF(1-29) sequence, and they are usually described as D-Ala at position 2, Gln at position 8, Ala at position 15 and Leu at position 27. They fall into three functional classes and it is a mistake to treat them as one undifferentiated set of tweaks.

The first class is protease blockade. Dipeptidyl peptidase-4 cleaves after the residue in position 2 and requires an L-configured alanine or proline there. Substituting the D-enantiomer at that single position inverts the stereochemistry the enzyme has to recognize and the cleavage effectively stops. This is the same design move used at the N-terminus of the incretin analogs elsewhere in this catalog, executed with a D-amino acid rather than with alpha-aminoisobutyric acid, and it is responsible for most of the difference in persistence between this peptide and plain sermorelin.

The second class is chemical liability removal, and it is the one most often skipped in vendor descriptions. Position 8 in the native sequence is an asparagine, and asparagine residues followed by small flexible neighbors are the classic site for deamidation through a cyclic succinimide intermediate, which converts the residue to a mixture of aspartate and isoaspartate and quietly generates a family of variants with the same nominal mass region. Replacing it with glutamine removes that route. Position 27 in the native sequence is a methionine, the most readily oxidized residue in the standard set, and replacing it with the isosteric leucine removes the sulfoxide pathway entirely. Neither substitution is about receptor binding; both are about the molecule staying one molecule.

The third class is affinity and conformation. The glycine-to-alanine change at position 15 sits in the amphipathic helix that the receptor reads, and glycine is the residue that most destabilizes helical structure. Adding a methyl group there stiffens the helix, and increased receptor affinity is the reported consequence.

Ipamorelin is structurally a different kind of object: a short C-terminally amidated pentapeptide containing alpha-aminoisobutyric acid and two D-configured aromatic residues, one of them a bulky naphthyl side chain. It is not a fragment of anything. Its protease resistance is intrinsic, a consequence of being built from residues that mammalian peptidases were never selected to cleave, and its aromatic bulk is what lets a five-residue chain occupy a receptor pocket evolved for an octanoylated 28-residue hormone.

The target and the pathway in more detail

The two components act at two different receptors that happen to sit on the same pituitary cell type, and the receptors are not related to each other in any structural sense.

Modified GRF(1-29) engages the GHRH receptor, a class B secretin-family G-protein-coupled receptor. Like the incretin receptors it couples principally to Gs, so activation raises intracellular cyclic AMP, activates protein kinase A and drives both the immediate release of stored granules and, over a longer timescale, transcriptional effects through CREB on growth hormone gene expression and on somatotroph proliferation. The binding mode is the standard two-domain one for this receptor class: the large extracellular domain captures the C-terminal helix of the ligand, and the ligand N-terminus inserts into the transmembrane bundle to trigger activation. This is exactly why the first two or three residues are so sensitive to modification and why an N-terminally truncated GHRH fragment loses activity while a C-terminally truncated one does not.

Ipamorelin engages the growth hormone secretagogue receptor type 1a, the receptor for ghrelin. This is a class A rhodopsin-family receptor and it couples principally to Gq/11, so activation runs through phospholipase C, inositol trisphosphate and a rise in intracellular calcium rather than through cyclic AMP. GHS-R1a is additionally notable in the literature for a high level of constitutive activity in the absence of ligand, which is a genuine complication when interpreting antagonist and inverse agonist data at this receptor. Its native ligand carries an octanoyl group on serine 3 that is required for activity, and the synthetic secretagogues reproduce that hydrophobic requirement with aromatic side chains instead.

The published rationale for combining the two rests on the fact that these are convergent but mechanistically distinct inputs to the same cell, with a third input, somatostatin acting through its own inhibitory receptors, running against both. Growth hormone secretagogues are reported to act in part by opposing that somatostatin tone as well as by direct stimulation, which is the usual explanation offered for why the combined response exceeds the arithmetic sum of the separate responses. There is also a hypothalamic component in intact animals, since GHS-R1a is expressed on GHRH-producing neurons, so an intact-animal result and an isolated-pituitary-cell result are answering different questions and should not be pooled.

What the published literature on CJC-1295 / Ipamorelin actually measures

The literature relevant to this vial is really three literatures, and the weakest of them is the one about the actual blend.

The deepest and oldest body of work concerns GHRH and its truncated fragments, and it is largely classical endocrine pharmacology: receptor binding and cyclic AMP accumulation in pituitary preparations, secretory response in perifused or dispersed somatotroph cultures, and characterization of the receptor itself after it was cloned. Modified GRF(1-29) enters this literature mainly as a stabilized tool, and the more informative papers are the medicinal-chemistry reports that compare the substituted analog against the parent fragment in the same assay and attribute the difference to specific residues. Those side-by-side comparisons are the most useful citations for this component, because they are internally controlled.

The second body of work concerns the growth hormone secretagogues, and it is substantially larger than most buyers expect. It runs from the original enkephalin-derived hexapeptides through GHRP-6 and hexarelin to the identification of GHS-R1a as an orphan receptor and then to the discovery of ghrelin as its endogenous ligand, which reframed the entire field retroactively. Ipamorelin's own primary literature is a much smaller slice of this: a founding pharmacological description reporting selective growth hormone release with comparatively little effect on the corticotropic and lactotropic axes in the models tested, followed by a modest number of animal studies in bone, gastric motility and catabolic models. It is not a heavily used tool compound in current academic work.

The third body of work is the combination itself, and here the honest statement is that most of what is cited is not about this pair. The classical demonstrations that a GHRH peptide plus a secretagogue peptide produce a supra-additive secretory response were done with native GHRH or sermorelin together with GHRP-6 or hexarelin, in human physiology studies and in animal and pituitary-cell preparations, largely in the 1980s and 1990s. Controlled published work using specifically modified GRF(1-29) plus specifically ipamorelin, in a fixed 1:1 mass ratio, in a defined preparation, is close to absent. The combination is a reasonable extrapolation from receptor logic. It is not an experimentally established finding for this exact pair, and the distinction matters when you write a methods section.

Where the CJC-1295 / Ipamorelin literature is thin or frequently misread

The single largest source of error in secondary material about this compound is the with-DAC versus without-DAC distinction, and it is worth stating bluntly. The Drug Affinity Complex is a maleimidoproline group attached through an added C-terminal residue. Its purpose is to react with the free cysteine thiol on circulating serum albumin and form a covalent bond, so the peptide is no longer a free peptide at all but a permanent albumin conjugate that persists on the order of days. Without that group, the peptide is a short-lived molecule whose persistence is measured in minutes to a small number of hours. These are not two grades of the same product. They produce different time-courses, different secretory profiles and different experimental designs, and a study built around one is uninformative about the other.

The trap is that an enormous quantity of published discussion, vendor copy and forum material simply says CJC-1295 without specifying which form is meant. Half-life figures quoted in days almost certainly refer to the DAC construct. Descriptions of a short pulsatile response almost certainly refer to this one. When you encounter a figure with no qualifier, treat the citation as unusable until you can establish which molecule was in the vial.

The second area of thin evidence is the synergy claim. The idea that GHRH-receptor and ghrelin-receptor stimulation combine more than additively is genuinely supported by older physiology, but that support comes from a different pair of compounds. The specific numeric multipliers that circulate for this blend, the assertions that the combination produces some particular fold increase over either component, are not traceable to a controlled study of this pair and should be treated as folklore rather than data.

Third, ipamorelin's selectivity claim is real but bounded. It rests on preclinical comparisons against GHRP-6 and hexarelin under specific conditions, and selectivity measured against those comparators at those concentrations does not generalize to an absolute absence of cross-axis activity. Reporting it as selective is accurate; reporting it as having no effect on other axes overstates what was measured.

How CJC-1295 / Ipamorelin behaves in solution

Both components arrive as lyophilized solids and, unusually for this catalog, they arrive mixed. A co-lyophilized cake is a single physical object, so anything you do to it you do to both peptides at once, and their properties are not the same.

The GHRH component is a 29-residue amphipathic helix with a substantial complement of charged residues and behaves like a conventional medium-length peptide in aqueous solution: readily soluble in water at neutral to slightly acidic pH, with the usual medium-peptide caveats about adsorption to glass and untreated plastic at low concentration. Its two classic degradation routes have been deliberately engineered out, which is a genuine practical advantage of this analog over plain sermorelin. The asparagine at position 8 that would otherwise deamidate through a succinimide intermediate has been replaced, and the methionine at position 27 that would otherwise oxidize to the sulfoxide has been replaced. The substitutions were made for stability in plasma, but they remove exactly the two processes that most often degrade a peptide sitting in a vial, so the benefit carries over to the bench.

The pentapeptide component is more hydrophobic per unit mass because of its two aromatic side chains, one of them a naphthyl group, and its C-terminal amide removes a charge that would otherwise aid solubility. In practice it dissolves without difficulty, but in a mixed cake the two components do not necessarily wet and dissolve at the same rate, and incomplete or hurried reconstitution can leave a solution that is enriched in one component relative to the other. Allowing the cake to dissolve fully without agitation is more important for a blend than for a single peptide, and vigorous shaking is worse than useless because the air-water interface is where peptides denature.

Freeze-thaw cycling is the usual dominant loss mechanism and it acts on both components, though not equally. A solution that has degraded typically shows faint haze or fine particulates against a dark background before anything is measurable by absorbance, and a blend can go cloudy from one component while the other is still fine. The storage figures printed in the specification table above are the product record for this material and should be read against the documentation supplied with the lot.

Analytical notes specific to CJC-1295 / Ipamorelin

The analytical problem specific to this listing is that the vial contains two chemically unrelated substances and most routine checks only ever see one of them. This is worth working through carefully, because it is the point on which blend documentation most often falls short.

Start with what gross weight tells you, which is almost nothing. Weighing the cake, or trusting the labeled total, confirms only that some quantity of solid is present. It cannot distinguish a correct 5 mg plus 5 mg fill from a 9 mg plus 1 mg fill, and it cannot distinguish either from 10 mg of one component with the other absent. The stated ratio is an assertion about composition and gross mass is not a measurement of composition.

Mass spectrometry as usually reported is similarly incomplete. A certificate that gives a single observed mass has, at best, confirmed the identity of one component. Because the two peptides differ enormously in size, a 29-residue chain against a five-residue chain, they behave very differently in electrospray: the larger one produces a multiply charged envelope requiring deconvolution while the pentapeptide appears as a small number of low-charge-state ions, and depending on the acquisition range and the tuning one of them can be missed entirely. What is actually required is either two separately reported observed masses or, better, an LC-MS run reported as two extracted ion chromatograms, one per component, so that presence and retention time are established independently for each.

Chromatography can address the ratio, but only if it is read correctly. Two peptides this different in hydrophobicity will resolve easily on a reversed-phase gradient, so a properly reported trace should show two well-separated main peaks with an area ratio, not a single purity percentage. The critical subtlety is that area at low ultraviolet wavelengths tracks amide bond absorbance, so response scales roughly with chain length, and an equal-mass blend of a 29-mer and a 5-mer will not produce anything close to equal peak areas. Reading a lopsided area ratio as evidence of a wrong fill is a common and avoidable error. Interpreting the ratio requires either response factors established from the individual reference materials or a detection method that is closer to mass-proportional, and either way the method has to be stated. Orthogonal confirmation, chromatographic separation plus component-specific mass identification, is the only thing that actually establishes that both peptides are present at the stated proportion.

Compounds researchers confuse with CJC-1295 / Ipamorelin

Questions specific to CJC-1295 / Ipamorelin