CJC-1295 (no DAC) + Ipamorelin: Two Peptides, Two Receptors, One Vial

CJC-1295 (no DAC) with Ipamorelin is not one compound. It is a blend of two synthetic peptides, packaged together because they act on two different receptors that converge on the same pituitary cell type. Echo supplies the pair as a lyophilized powder, 5 mg of each peptide in a 10 mg vial, strictly as a reference material for in-vitro and preclinical laboratory work. This guide describes what each component is, what the published literature actually establishes about the receptors they engage, and — a longer list than researchers usually expect — what it does not.

Two cautions belong at the top, because they shape everything below. First, the name "CJC-1295 (no DAC)" is used inconsistently in the primary literature, and a researcher who searches the name alone will retrieve papers about a chemically different molecule. Second, almost nothing in the peer-reviewed record examines this blend as a blend. The evidence base is about the individual peptides, and mostly about their receptors.

Why this product carries no identity block

Echo publishes a verified identity block — CAS number, molecular formula, molecular weight, PubChem CID — for single-compound products, drawn from a checked internal map rather than typed from memory. This product has no such block, and the reason is chemical rather than administrative: a mixture has no molecular identity. There is no CAS registry number for "CJC-1295 plus ipamorelin," no combined formula, and no single molecular weight, because those descriptors apply to defined molecular entities and a blend is not one. Any figure presented as the molecular weight of this product would be an invention.

What can be said structurally comes from the primary literature on each peptide. Ipamorelin is a pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH₂, identified within a series of compounds that lack the central Ala-Trp dipeptide of growth hormone-releasing peptide-1 ^[1]. The GHRH-analog component is based on human growth hormone-releasing factor, hGRF(1-29). The compound named CJC-1295 in the primary literature is described there as a tetrasubstituted form of that 29-residue peptide with an added Nε-3-maleimidopropionamide derivative of lysine at the C terminus ^[2]; reading the blend's component as that tetrasubstituted parent minus the added lysine is this guide's mapping, not the paper's. Neither of these is an identity number, and neither should be treated as one. A Certificate of Analysis for a blend should establish the identity and purity of both components separately; a single purity figure for a two-peptide mixture describes nothing verifiable.

The naming problem behind "no DAC"

This is the point most likely to cause a researcher to cite the wrong paper. The designation CJC-1295 was introduced in a 2005 study that screened three maleimido derivatives of hGRF(1-29) for the ability to form a covalent bioconjugate with the free thiol on Cys34 of serum albumin. The compound the authors selected and named CJC-1295 was a tetrasubstituted hGRF(1-29) bearing an added Nε-3-maleimidopropionamide derivative of lysine at the C terminus. That albumin-reactive maleimide is what the later analytical literature calls the drug affinity complex; neither paper states the equivalence in its abstract — the 2005 abstract does not use the term at all, and the 2021 abstract uses it only inside a compound name — so that identification is this guide's reading rather than a sourced claim ^{[2, 3]}. All three albumin conjugates showed enhanced in-vitro stability against dipeptidyl peptidase-IV and were bioactive in a growth hormone (GH) secretion assay in cultured rat anterior pituitary cells. The selected compound was found in rat plasma beyond 72 hours ^[2].

On that reading, in the paper that named it, CJC-1295 is the DAC-bearing molecule. "CJC-1295 no DAC" is therefore, read against that source, a description of what the compound is missing.

Later analytical literature uses the name the other way. A 2021 anti-doping study investigating the in-vitro metabolism and mass-spectrometric detection of GHRH synthetic analogs treats "CJC-1295" and "CJC-1295 with drug affinity complex" as two separate target peptides alongside sermorelin and tesamorelin, synthesizing and characterizing nineteen major in-vitro metabolites as reference materials ^[3]. That usage — one name for the parent analog, the other for the albumin-reactive conjugate — matches how the material sold under this name is generally understood, though the abstract sets out no structure for either entry, so the mapping is again this guide's reading ^[3].

The practical consequence: pharmacokinetic findings reported for CJC-1295 in the 2005 conjugation study describe a molecule with an albumin-binding group. They do not transfer to a peptide that lacks one, and the extended plasma presence reported there is a property of the conjugation strategy. Any literature search on this component should specify which form is meant.

The GHRH receptor

The GHRH receptor is a class B G protein-coupled receptor expressed on pituitary somatotrophs. A 2020 cryo-electron microscopy study resolved the human receptor bound to its endogenous ligand and the stimulatory G protein at 2.6 Å, showing that α-helical GHRH forms a continuous interaction network involving the receptor's extracellular domain, all of its extracellular loops, and every transmembrane helix except TM4, with the N-terminus of the hormone making a broad set of specific contacts ^[4]. The structure was solved with native GHRH, not with a synthetic analog, so it describes how the receptor recognizes its endogenous ligand rather than the binding pose of any GHRH analog.

Ipamorelin and the ghrelin receptor

Ipamorelin acts through a different receptor entirely: GHS-R1a, the ghrelin receptor, a seven-transmembrane receptor for which the endogenous ligand is acyl-ghrelin. The original 1998 characterization reported that ipamorelin released GH from primary rat pituitary cells with potency and efficacy similar to GHRP-6, and that pharmacological profiling with GHRP and GHRH antagonists indicated the effect ran through a GHRP-like receptor rather than the GHRH receptor ^[1]. A companion program characterizing NN703, a secretagogue derived from ipamorelin, found that its GH-releasing effect in rat pituitary cells was inhibited by known GHS antagonists but not by a GHRH antagonist, and that it competed with ³⁵S-MK677 binding at the human type 1A GHS receptor stably expressed in BHK cells ^[6].

The receptor itself has since been resolved structurally. Cryo-EM structures of the human GHSR–Gi signaling complex with ghrelin and with the non-peptide agonist ibutamoren, together with mutagenesis data, reveal the molecular basis for the binding of both ligands, and structural comparison suggests a salt bridge and an aromatic cluster near the agonist-binding pocket as important structural motifs in receptor activation ^[5]. Ipamorelin was not among the ligands in that work, so the structures describe the pocket it is presumed to occupy rather than its own binding mode.

GHSR1a is also not a single-output receptor. Work on a functionally selective small-molecule ligand characterizes GHSR1a activation as producing pleiotropic outcomes through distinct and pharmacologically separable G protein- and β-arrestin-dependent pathways, which is the premise on which biased ligands for this receptor are designed ^[12]. Any assay that reads only one branch — a G protein readout alone, or β-arrestin recruitment alone — is measuring part of the receptor's behavior.

The selectivity finding

The result that made ipamorelin notable is a negative one. In swine, none of the GH secretagogues tested altered FSH, LH, prolactin, or TSH; but GHRP-6 and GHRP-2 both raised plasma ACTH and cortisol, whereas ipamorelin did not raise them to levels significantly different from those seen after GHRH stimulation, and this held across the exposure range examined ^[1]. The authors described the finding as surprising and framed ipamorelin as the first GHRP-receptor agonist with GH-release selectivity comparable to GHRH. Two limits belong with it: the observation is in one species, and it is about ACTH and cortisol specifically. It is not a general claim that the compound has no off-target activity.

Structure-activity work

Ipamorelin has been used as a starting point in medicinal chemistry more often than it has been studied as an endpoint. A structure-activity study of peptidic secretagogues examined several GHRPs and truncated analogs sharing an Ala-Trp-(D-Phe)-Lys core in a radio-competitive GHSR1a assay against radiolabeled ghrelin, reporting the chemical modifications at positions 1, 2, 3, and 7 of that scaffold that influence activity ^[7]. Ipamorelin does not carry that core — it came out of the series lacking the central Ala-Trp dipeptide ^[1] — and in that study it figures in a separate arm, which confirmed that receptor-assay activity is recoverable from excretion samples ^[7]. A series of NN703 analogs combining lysine mimetics with naphthyl- or biphenylalanine in the core produced compounds more potent than expected in a rat pituitary cell assay ^[8]. More recently, the ipamorelin backbone was used as a scaffold for boron-rich carborane conjugates built as ghrelin receptor ligands ^[9]. The common thread is that ipamorelin has served more often as a chemical starting point than as the object of study.

Two receptors, one cell type

The rationale for pairing a GHRH analog with a ghrelin-receptor agonist rests on the claim that the two act at distinct sites. There is direct in-vitro evidence for that separation, though not with these two peptides. In a 1997 study, hexarelin — a GHRP-6 analog, not ipamorelin — stimulated GH release both in normal rat pituitary cells and in the GH1 rat tumor cell line, which does not respond to GHRH. In normal rat somatotrophs, GHRH and hexarelin had additive stimulatory effects on GH secretion; in GH1 cells, GHRH did not modify the hexarelin response at any concentration tested. The authors read this as in-vitro evidence that non-GHRH-mediated pathways for GHRP action exist, and wrote that the stimulation of GHRH-insensitive cells by hexarelin strongly suggests that GHRPs and GHRH have two distinct sites and modes of action at the pituitary level ^[10]. That reading is about the compound classes, and extending it to this specific pair is an inference, not a finding.

There is a second potential site of action above the pituitary. Recordings in transgenic GHRH-GFP mice showed that ghrelin increases the firing rate of identified GHRH neurons in the arcuate nucleus through a direct depolarizing effect: the response was prevented by a GHS-R1 antagonist, by a phospholipase C inhibitor, and by calcium channel blockers, was not abolished by GABA, glutamate, or NPY receptor antagonists, and persisted in somatostatin knockout mice ^[11]. The ligand there was ghrelin itself, not ipamorelin, and the site was the hypothalamus rather than the pituitary — so this describes a mechanism available to ghrelin-receptor agonists in an intact nervous system, not a demonstrated property of this blend.

What preclinical work exists on ipamorelin

Beyond receptor pharmacology, the animal literature on ipamorelin is thin and mostly old. One controlled study in thirteen-week-old female Sprague-Dawley rats compared ipamorelin, GHRP-6, GH, and vehicle over twelve weeks, following animals in vivo by dual X-ray absorptiometry and analyzing excised bone by peripheral quantitative computed tomography, Archimedes' principle, and ash weight. All treatments increased total tibial and vertebral bone mineral content relative to vehicle. The authors were explicit about what that did and did not mean: total bone mineral content corrected for body weight was unaffected, cortical volumetric bone mineral density was unchanged, as were the volumetric densities determined by Archimedes' principle, and the increases in cortical and total bone mineral content were attributable to increased cross-sectional bone area and larger bone dimensions rather than to denser bone ^[13]. Reporting the headline without the correction misrepresents the paper.

What is not established

This section is the honest center of the guide.

• The blend has not been characterized as a blend. Published work examines these peptides individually. There is no primary study establishing what the fixed 1:1 combination does in any model system, and no basis in the literature for the particular ratio.
• Synergy is a hypothesis carried over from other compounds. The additive-effect evidence at the pituitary comes from hexarelin and GHRH in rat cells ^[10], not from ipamorelin and a GRF(1-29) analog. Whether the same relationship holds for this pair, in which system, and whether it is additive or more than additive, has not been shown.
• The GHRH-analog component is under-characterized in its non-conjugated form. The most-cited pharmacokinetic result for CJC-1295 is a property of albumin conjugation ^[2], and much of what is published about the unconjugated peptide comes from analytical and anti-doping chemistry — metabolite identification and detection limits — rather than receptor pharmacology ^[3].
• Structures do not exist for these ligands. The high-resolution structures available are of GHRHR with native GHRH ^[4] and of GHSR with ghrelin and ibutamoren ^[5]. Neither ipamorelin nor a GRF(1-29) analog appears in a solved complex, so binding poses for the components of this blend are modeled, not observed.
• Species and preparation matter. The selectivity result is from swine ^[1], the potency comparisons from primary rat pituitary cells ^{[1, 6]}, the bone study from rats ^[13], the GHRH-neuron recordings from mice ^[11]. Cross-species extrapolation of secretagogue pharmacology is not automatic.
• Nothing here addresses human or veterinary outcomes, and this guide makes no statement about them. Administration of GHRH and its synthetic analogs is prohibited by the World Anti-Doping Agency ^[3], and peptidic secretagogues are studied in the same anti-doping context ^[7]; that is why much of the recent analytical literature on these peptides exists at all.

Practical notes for laboratory characterization

Because the material is a mixture, several ordinary quality questions become two questions. Identity confirmation should resolve both peptides — they differ enormously in size, so a single chromatographic peak is a red flag rather than a sign of purity. Purity should be reported per component, and the stated ratio should be something the analysis supports rather than something the label asserts. Mass-spectrometric methods developed in the anti-doping context for the GHRH analogs, including nineteen in-vitro metabolites synthesized and characterized as reference materials, provide a published starting point for identifying metabolites as well as the parent compound for that component of the blend ^[3].

Assay design should follow the receptor split. The GHRH receptor was resolved in complex with the stimulatory G protein ^[4], while GHSR1a signals through distinct and pharmacologically separable G protein- and β-arrestin-dependent pathways ^[12], so no single readout reports both arms. Antagonist controls are the cleanest way to attribute a signal to one component or the other, and this is exactly how the original characterizations distinguished the two pathways ^{[1, 6]}. Radio-competitive binding against radiolabeled ghrelin is the assay used for the GHSR1a arm in that structure-activity work ^[7].

Store the lyophilized material refrigerated at 2–8 °C, protected from light and moisture, consistent with the product's stated handling conditions.

This material is supplied for research use only. It is not intended for human consumption, veterinary use, or any clinical application, and it has not been evaluated by the FDA. Nothing in this guide describes or implies use in humans or animals outside a controlled laboratory setting.