The Hulk Stack: a two-peptide GH-axis research set

The Hulk Stack is a 20mg research blend of two peptides: CJC-1295 with DAC, an albumin-reactive analog of growth-hormone-releasing hormone, and ipamorelin, a five-residue ligand of the ghrelin receptor. If you arrived here after searching for "CJC-1295 ipamorelin", one fact matters more than any other. Most products sold under that name pair ipamorelin with CJC-1295 without DAC, a molecule also known as Mod GRF (1-29). The Hulk Stack is the other version, built on the DAC-modified analog. The two GHRH-side molecules differ in mass, in reactive chemistry and in how long they survive in a biological matrix, so they answer different research questions. Below: what the DAC actually is, how each component reaches its receptor, what cell-level work has measured, and what to check before buying the Hulk Stack in the United States.

Research use only. The Hulk Stack is sold for in-vitro laboratory work. It is not for human or veterinary use, it has not been evaluated by the FDA, and nothing on this page is an instruction for use in people or animals.

Where the Hulk Stack fits among CJC-1295 and ipamorelin products

Three GHRH-side molecules appear in US listings next to ipamorelin, and their names overlap enough to cause genuine mix-ups:

The first row, paired with ipamorelin, is what most "CJC-1295/ipamorelin" listings mean, and our CJC-1295 and ipamorelin guide covers that pairing. The second row is the Hulk Stack. Tesamorelin is a separate, full-length GHRH analog that we sell on its own as Tesamorelin; it is not part of any blend.

The working rule follows from the table. A protocol written around an unconjugated, quickly cleared GRF analog cannot swap in the Hulk Stack and expect comparable behavior. A protocol that needs the albumin-binding chemistry cannot get it from the no-DAC pairing.

What "DAC" means at the bench

DAC stands for drug affinity complex, the name ConjuChem, the Montreal company that developed CJC-1295, gave its albumin-binding technology. Chemically it is a small addition: a lysine placed after residue 29, carrying a 3-maleimidopropionyl group on its side-chain (epsilon) amine. Everything implied by the "long-acting" description comes from that maleimide.

A maleimide is an electron-poor five-membered ring that reacts selectively with thiols. A free sulfhydryl adds across its carbon-carbon double bond, a Michael addition, and leaves a thioether called a thiosuccinimide. Serum albumin has exactly one free thiol, on cysteine 34, and ConjuChem's design used it as the docking point. In the group's 2005 Endocrinology paper, three maleimide derivatives of GRF(1-29) were conjugated to human serum albumin outside the body; the conjugates were clearly more stable against DPP-4 in vitro and still activated the GRF receptor in cultured rat pituitary cells, and CJC-1295 was the derivative selected from that series. A year earlier the same team had applied the same chemistry to a GLP-1 analog, CJC-1131. DAC is a conjugation platform, not something peculiar to GHRH.

Three practical consequences follow for anyone handling the material:

1. The vial holds the unconjugated peptide. Albumin binding is something the maleimide does once it meets a thiol. Until then the reactive ring has to stay intact for the molecule to be what its name claims.
2. Maleimides hydrolyze. In water the ring can open to a maleamic acid. That adds 18 Da and removes the thiol reactivity while leaving the rest of the peptide untouched, and it proceeds faster as pH rises. A mass spectrum that separates the intact species from a +18 Da shoulder is the direct check.
3. Thiol additives compete. Reducing agents such as DTT and β-mercaptoethanol, and free cysteine or glutathione, all react with maleimides. A buffer containing them will use up the DAC group before an experiment begins.

The thioether, once formed, is not permanent either. Bioconjugation chemists have measured two competing reactions for maleimide-thiol adducts: thiol exchange, which can hand the attached molecule over to a different thiol, and hydrolytic opening of the succinimide ring, which locks the adduct in place. Which one wins depends on the substituent on the maleimide nitrogen.

The backbone: four substitutions on GRF(1-29)

Native growth-hormone-releasing hormone is 44 residues long, but its first 29 carry the receptor activity, which is why most synthetic analogs start from GRF(1-29). The native sequence has a weak point at its N-terminus. In a 1986 study, the full hormone incubated with human plasma disappeared with a half-life of about 17 minutes by HPLC, cleaved to GRF(3-44), a fragment with less than a thousandth of the parent's activity. The plasma dipeptidyl aminopeptidase responsible is the enzyme now called DPP-4.

Both CJC-1295 variants carry the same four changes to the 1-29 backbone, each aimed at a known chemical weakness:

So the two CJC-1295 forms are identical across their first 29 residues. The DAC version differs only by the added lysine and its maleimide, about 279 Da, but that small appendage decides how the molecule behaves anywhere albumin is present.

Two receptors, two signaling routes

The two components are ligands for receptor families that share a cell type, the pituitary somatotroph, and very little else.

The GHRH receptor. Cloned from human pituitary in 1993, it is a 423-amino-acid G-protein-coupled receptor of the secretin family (class B), related to the receptors for VIP, secretin, calcitonin and parathyroid hormone. Its main coupling is to adenylyl cyclase, so activation raises intracellular cAMP. CJC-1295, in either form, is an agonist here.

The ghrelin receptor, GHSR-1a. This one was cloned in 1996 from pituitary and hypothalamus as the target of synthetic growth-hormone secretagogues, before anyone knew its natural ligand. That ligand, ghrelin, was isolated from rat stomach in 1999: a 28-residue peptide whose serine 3 carries an n-octanoyl group that is essential for activity. GHSR-1a is a class A (rhodopsin-like) receptor that signals mainly through phospholipase C, raising calcium and diacylglycerol rather than cAMP. It is also unusually busy with no ligand bound: in transfected cells it shows strong constitutive signaling, which a 2003 study suppressed with an inverse agonist.

Ipamorelin is a GHSR agonist, and its sequence, Aib-His-D-2-Nal-D-Phe-Lys-NH₂, shows where it came from. It emerged from a Novo Nordisk chemistry program built around the growth-hormone-releasing peptide GHRP-1, within a series that dropped GHRP-1's central Ala-Trp dipeptide. Its original characterization included primary rat pituitary cells in vitro, and pharmacological profiling with GHRP and GHRH antagonists placed its action at the GHRP-type receptor rather than the GHRH receptor. Three of its five residues are non-proteinogenic (Aib, D-2-naphthylalanine and D-phenylalanine), which makes it a demanding synthesis and a molecule in which epimerized or truncated impurities are worth looking for.

What the two-receptor cell work has measured

Pairing a GHRH-receptor agonist with a GHSR agonist is not only a catalog habit. There is a defined in-vitro question underneath it, and the clearest experiment on that question was run in engineered cells.

In a 2002 study, Cunha and Mayo expressed the cloned GHRH receptor and GHS receptor together in a single homogeneous cell line and measured cAMP. Activating the GHS receptor on its own did not change cAMP. Activating both produced roughly twice the cAMP seen with the GHRH receptor alone. The amplification needed both receptors present, was not blocked by inhibiting the usual GHSR pathway (G-protein βγ subunits, phospholipase C, protein kinase C) and was specific: cAMP raised by forskolin, or through the related VIP and secretin receptors, was not amplified by GHSR activation. The authors proposed a direct interaction between the two receptors.

That is the kind of question a two-component blend can probe: cross-talk between a Gs-coupled class B receptor and a Gq-coupled class A receptor in one cell. Two cautions apply. The 2002 work used GHRH with ghrelin and a range of synthetic secretagogues; it was not a study of CJC-1295 with DAC or of this blend. And no controlled study of the Hulk Stack itself has been published, so what the literature offers is single-compound pharmacology plus receptor-level experiments like this one.

Albumin in the dish: a variable people miss

Because the DAC group exists to react with albumin, the culture medium becomes part of the experiment. Fetal bovine serum contains bovine serum albumin, which, like the human protein, has a single free cysteine at position 34. In a serum-containing medium, a share of the CJC-1295 with DAC can be expected to end up covalently bound to that albumin; in a serum-free medium it stays free unless another thiol reaches it first. Any comparison between the two conditions, or against a no-DAC analog, should state the serum content and, where possible, confirm which species is present, for example by mass spectrometry or by a Western blot against the albumin band, the approach used in the original ConjuChem work.

The two members of the blend part ways here. Ipamorelin has no thiol-reactive group and does not form this covalent link, so serum content changes the free concentration of one component and not the other.

Reading a certificate for a two-peptide blend

One purity percentage cannot describe a vial holding two different molecules. For the Hulk Stack, a batch certificate earns trust when it shows:

• Two identity results. The components are about 2,935 Da apart and differ widely in hydrophobicity, so reversed-phase HPLC and electrospray mass spectrometry resolve them easily. Expect roughly 3,647 Da for CJC-1295 with DAC and roughly 712 Da for ipamorelin.
• An intact maleimide. The CJC-1295 result should be the intact species, without a dominant +18 Da ring-opened peak.
• Purity for each component, measured against its own peak rather than blended into one figure.
• A clear basis for the stated amount. Our listing gives 20mg as the total for the blend; any per-component figure belongs on the listing or certificate, not in a guide.
• A lot number that matches the vial. A certificate for a different batch describes a different material.

Our batch certificates are in the COA library, and the Certificate of Analysis guide walks through each section.

Buying the Hulk Stack in the United States

Whoever supplies it, a Hulk Stack listing should name the DAC status outright. "CJC-1295" on its own is ambiguous, and a listing that leaves the variant unstated cannot be compared with anything.

Our Hulk Stack is CJC-1295 with DAC plus ipamorelin, 20mg in total. It is dispatched cold-chain from the warehouse that serves the United States, with tracked delivery across the country next business day, priced in US dollars and payable by Visa, Mastercard or Apple Pay. Keep it refrigerated at 2-8°C, sealed and away from light. We sell the two peptides only as this blend: the US CJC-1295 and ipamorelin singles are no longer listed, so for each compound on its own, read What is CJC-1295? and What is ipamorelin?.

Regulatory and anti-doping status

• Not an approved drug. Neither CJC-1295, in either form, nor ipamorelin is an FDA-approved drug, and the Hulk Stack has not been evaluated by the FDA. It is sold for in-vitro laboratory research and is not for human or veterinary use.
• WADA. Growth-hormone secretagogues and GHRH analogs, including GHS-R agonists, fall under class S2 of the WADA Prohibited List. That matters to anyone working under anti-doping rules.

What this page leaves out

This guide gives no amounts, schedules or preparation-for-use instructions for the Hulk Stack or either component, and none will be added. The material is supplied for in-vitro research, and the concentrations used in published cell work are specific to each model and readout; the primary papers are the place to find them.

Related reading

• CJC-1295 and ipamorelin: the no-DAC pairing · What is CJC-1295? · What is ipamorelin? · What is tesamorelin? · How to read a Certificate of Analysis