What Is CJC-1295 no DAC? Complete Research Guide

## Introduction Growth hormone-releasing hormone (GHRH) is the hypothalamic signal that commands the pituitary gland to release growth hormone (GH) — but native GHRH is degraded in blood within minutes, which limits its usefulness as a research tool. CJC-1295 no DAC was engineered to solve exactly that problem: a synthetic analog of the first 29 amino acids of human GHRH, modified at four positions to resist enzymatic breakdown, while remaining a short-acting, pulsatile compound. Also known in the literature as Modified GRF 1-29 (or Mod GRF 1-29), CJC-1295 no DAC is its own distinct compound — not a weaker or partial version of something else, but a stabilized GHRH(1-29) analog with a reported half-life of approximately 30 minutes. Because it clears quickly, it produces discrete pulses of GH release that mirror the body's endogenous rhythm rather than sustained elevation. This guide reviews its chemical structure, the published rationale behind each of its four substitutions, its mechanism of action at the GHRH receptor, and the research record. All discussion is framed around laboratory research; CJC-1295 no DAC is a research compound and is not approved for human or veterinary use. ## What Is CJC-1295 no DAC? Chemical Structure CJC-1295 no DAC is a synthetic, tetrasubstituted analog of the N-terminal 29-amino-acid fragment of human growth hormone-releasing hormone — GHRH(1-29). Four residue positions in the natural sequence are altered: - **Position 2:** L-alanine replaced with **D-alanine** — blocks cleavage by the enzyme dipeptidyl peptidase-IV (DPP-IV) at the Tyr-Ala bond, the primary route of native GHRH degradation in plasma. - **Position 8:** glycine replaced with **glutamine** — reduces asparagine rearrangement and amide hydrolysis. - **Position 15:** glycine replaced with **alanine** — designed to enhance receptor binding and bioactivity. - **Position 27:** methionine replaced with **leucine** — prevents methionine oxidation during handling and storage. The resulting 29-residue sequence is **Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2**, with molecular formula **C₁₅₂H₂₅₂N₄₄O₄₂** and molecular weight of approximately **3,367.9 g/mol**. It is catalogued in PubChem as CJC1295 Without DAC (CID 91976842), confirming its identity as a chemically distinct entry from the albumin-binding form. As with the compound covered in our [What Is Ipamorelin? guide](/insights/what-is-ipamorelin), identity and purity of research-grade material are verified by high-performance liquid chromatography (HPLC) and mass spectrometry, with a batch-specific Certificate of Analysis. ## Why These Substitutions: The Published Rationale Each of the four modifications in CJC-1295 no DAC traces back to published work on GHRH stability — and the literature explains why a stabilized but still short-acting analog is useful in its own right. ### Native GHRH Is Cleaved Within Minutes Frohman (1986) demonstrated that native growth hormone-releasing hormone undergoes rapid enzymatic degradation by plasma both in vitro and in vivo, yielding a biologically inactive product cleaved at the NH2 terminus. This finding established the central design problem for every GHRH analog that followed: the N-terminal region that carries receptor-activating activity is also the region most vulnerable to plasma enzymes, particularly DPP-IV. > **Citation:** Frohman LA. "Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus." *J Clin Invest*. 1986;78(4):906-913. [PubMed PMID: 3093533](https://pubmed.ncbi.nlm.nih.gov/3093533/) ### The D-Alanine Substitution Extends Half-Life in Humans Soule, King, and Millar (1994) tested the key position-2 modification directly in humans. Ten normal men received constant intravenous infusions of either unmodified GHRH-(1-29)-NH2 or the D-Ala2 analog. The metabolic clearance rate of the D-Ala2 analog was significantly lower (21 vs 39.7 mL/kg/min), and its disappearance half-time was longer (6.7 vs 4.3 minutes) than the unmodified fragment. The authors concluded that the D-Ala2 substitution enhances biological activity specifically by reducing metabolic clearance — the exact mechanism built into CJC-1295 no DAC at position 2. > **Citation:** Soule S, King JA, Millar RP. "Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men." *J Clin Endocrinol Metab*. 1994;79(4):1208-1211. [PubMed PMID: 7962295](https://pubmed.ncbi.nlm.nih.gov/7962295/) ### Stabilized Analogs With Increased Enzymatic Resistance Izdebski (2002) reported a series of new potent hGH-RH analogs engineered for increased resistance to enzymatic degradation, extending the medicinal-chemistry program that produced the tetrasubstituted scaffold. This body of work underpins the remaining substitutions at positions 8, 15, and 27 — each targeting a distinct degradation or stability liability (rearrangement, hydrolysis, oxidation) while preserving the receptor-binding surface of the 1-29 fragment. > **Citation:** Izdebski J. "New potent hGH-RH analogues with increased resistance to enzymatic degradation." *J Pept Sci*. 2002;8(7):285-287. [PubMed PMID: 12148777](https://pubmed.ncbi.nlm.nih.gov/12148777/) Together, these studies describe the design logic of CJC-1295 no DAC: keep the molecule short-acting and pulsatile, but make each pulse reliable by protecting the peptide from the enzymes that destroy native GHRH within minutes. ## A Note on CJC-1295 With DAC: A Different Product CJC-1295 with DAC (Drug Affinity Complex) is a separate, different product — not a stronger version of the compound described in this guide. It carries an additional albumin-binding moiety that extends circulation to days, and it was identified as a long-lasting GRF analog in a distinct development program (Jetté et al., 2005, PMID: 15817669). The two products have different pharmacokinetic profiles and are not interchangeable. The remainder of this guide concerns only CJC-1295 no DAC. ## Mechanism of Action: The GHRH Receptor CJC-1295 no DAC acts as an agonist at the growth hormone-releasing hormone receptor (GHRHR), a G-protein-coupled receptor expressed on somatotroph cells of the anterior pituitary. When bound, it activates the adenylate cyclase–cAMP signaling cascade, which triggers both the synthesis and the release of growth hormone from pituitary stores. This places the compound upstream of GH itself in the somatotropic axis: it does not supply exogenous growth hormone but stimulates the endogenous production and release machinery, which then drives hepatic production of insulin-like growth factor-1 (IGF-1), the principal circulating mediator of GH activity. The pharmacokinetic profile is central to how researchers use this compound. With a reported half-life of approximately 30 minutes, CJC-1295 no DAC clears quickly enough that each administration produces a discrete GH pulse followed by a return to baseline. This preserves the pulsatile pattern of endogenous GH secretion — the physiological rhythm in which GH is released in bursts rather than as a continuous stream — making the compound a tool for studying pulsatile GH-axis signaling rather than sustained elevation. ## CJC-1295 no DAC vs Other GHRH Analogs **Vs tesamorelin:** Tesamorelin is a larger, 44-amino-acid GHRH analog (molecular weight ~5,136 g/mol) and the only FDA-approved GHRH analog in the United States. Its design centers on an N-terminal hexenoyl modification of the full-length GHRH sequence. Both compounds act through the same GHRH receptor, but tesamorelin retains the complete 44-residue native sequence while CJC-1295 no DAC is built on the truncated 29-residue active fragment with four stabilizing substitutions. See our [What Is Tesamorelin? guide](/insights/what-is-tesamorelin) for detail. **Vs sermorelin:** Sermorelin is unmodified GHRH(1-29)-NH2 — the natural 29-amino-acid fragment without any stabilizing substitutions. Historically used as a diagnostic agent for pituitary GH function, it is highly susceptible to DPP-IV cleavage and clears within minutes. CJC-1295 no DAC can be understood as the stabilized successor to this scaffold: the same 1-29 backbone, engineered at four positions to survive the enzymes that destroy sermorelin almost immediately. **Vs ipamorelin:** Different pathway entirely — ipamorelin is a ghrelin-receptor (GHSR-1a) agonist, not a GHRH analog. The two are frequently studied in combination to stimulate the GH axis through complementary receptors: the GHRH pathway and the ghrelin pathway converge on the somatotroph from different directions. For a detailed head-to-head, see our [CJC-1295 vs Ipamorelin comparison](/insights/cjc-1295-vs-ipamorelin). ## Research Applications In the laboratory, CJC-1295 no DAC is studied across several domains: - **GH-axis pharmacology:** GHRH receptor binding, cAMP signaling, and structure-activity relationships of tetrasubstituted GHRH(1-29) analogs. - **Pulsatile GH paradigms:** Investigating how discrete, short-lived GH pulses differentially affect downstream endpoints compared with sustained elevation. - **Peptide stabilization chemistry:** The four-substitution design as a case study in protecting bioactive peptides from DPP-IV cleavage, rearrangement, hydrolysis, and oxidation. - **Comparative GHRH analog research:** Head-to-head studies against tesamorelin, sermorelin, and unmodified GHRH(1-29) to map how individual substitutions change stability and activity. - **Dual-pathway GH research:** Combination studies with ghrelin-receptor agonists such as ipamorelin to investigate synergistic stimulation through the two complementary GH-release pathways. - **Analytical chemistry:** Method development for quantification of short-acting GHRH analogs, impurity profiling of substituted peptides, and stability assessment. ## Frequently Asked Questions ### What is CJC-1295 no DAC? CJC-1295 no DAC (also called Modified GRF 1-29) is a synthetic tetrasubstituted analog of the GHRH(1-29) fragment: Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2 (C₁₅₂H₂₅₂N₄₄O₄₂, ~3,367.9 g/mol). Four amino-acid substitutions protect it from the enzymes that degrade native GHRH within minutes. ### Is CJC-1295 no DAC the same as CJC-1295 with DAC? No. They are different products with different pharmacokinetic profiles. CJC-1295 no DAC is a short-acting analog with a reported half-life of approximately 30 minutes, producing pulsatile GH release. CJC-1295 with DAC carries an additional albumin-binding moiety that extends circulation to days. They are not interchangeable. ### What is the half-life of CJC-1295 no DAC? Published summaries report a half-life of approximately 30 minutes (at least 30 minutes), consistent with a short-acting, pulsatile GHRH analog. The four stabilizing substitutions extend its functional life well beyond native GHRH's minutes-long survival in plasma, but it clears far faster than long-acting analogs. ### What receptor does CJC-1295 no DAC act on? It is an agonist of the growth hormone-releasing hormone receptor (GHRHR), a G-protein-coupled receptor on pituitary somatotrophs. Activation stimulates the adenylate cyclase–cAMP cascade, triggering GH synthesis and release. ### What is the purity of research-grade CJC-1295 no DAC? Reputable suppliers provide CJC-1295 no DAC at ≥99% purity verified by HPLC with mass spectrometry identity confirmation, accompanied by a batch-specific Certificate of Analysis. [Browse the COA library](/coas) for examples of published certificates. ## Conclusion CJC-1295 no DAC stands on its own as a research compound: a tetrasubstituted GHRH(1-29) analog — Modified GRF 1-29 — engineered at four positions to resist the enzymatic degradation that destroys native GHRH within minutes, while remaining a short-acting, pulsatile tool. The published record behind its design, from Frohman's degradation work through Soule's D-Ala2 human data to Izdebski's stabilized analogs, gives researchers a clear mechanistic rationale for each substitution. Its ~30-minute half-life makes it the instrument of choice for studying discrete GH pulses through the GHRH receptor, distinct in both identity and behavior from the long-acting DAC product that shares part of its name. For researchers sourcing CJC-1295 no DAC for laboratory use, verify ≥99% purity by HPLC, require mass spectrometry identity confirmation, and insist on a batch-specific Certificate of Analysis from an accredited laboratory. --- **Internal link suggestions:** - Product: [CJC-1295 no DAC 10MG](/product/cjc-1295-no-dac-10mg) - Related guide: [CJC-1295 vs Ipamorelin](/insights/cjc-1295-vs-ipamorelin) - COA library: [Browse certificates](/coas) For laboratory research use only. Not for human or veterinary use.