For Research Use Only. CJC-1295 (no DAC) is intended exclusively for in vitro and preclinical research. It is not approved for human use, is not a drug, and should never be administered to humans or to animals outside of a formal research protocol.
What Is CJC-1295 (No DAC)?
CJC-1295 is a tetrasubstituted analog of growth hormone releasing hormone (GHRH), a 44 amino acid neuropeptide that is the primary endogenous regulator of growth hormone release from the anterior pituitary. CJC-1295 retains the active fragment of GHRH (specifically the N-terminal 29 amino acids that constitute the GHRH(1-29) sequence) and incorporates four amino acid substitutions designed to protect the molecule from enzymatic degradation by dipeptidyl peptidase IV (DPP-IV) and other proteases that rapidly clear natural GHRH in research models.
The "no DAC" designation refers to the absence of the drug affinity complex modification that is present in the alternative CJC-1295 with DAC formulation. The DAC modification is a maleimido propionic acid linker that allows CJC-1295 to bind covalently to circulating serum albumin, dramatically extending the functional half life of the peptide in research animals. CJC-1295 with DAC has a half life measured in days, while CJC-1295 (no DAC) has a half life measured in minutes to hours. This difference is the foundation for their distinct research applications.
The stabilizing substitutions in CJC-1295 (no DAC) protect the peptide from proteolytic degradation but do not extend its half life through albumin binding. This makes CJC-1295 (no DAC) functionally similar to a more stable version of natural GHRH, with the practical advantage of being easier to handle in research settings while preserving the pulsatile release pattern that more closely mimics endogenous GHRH activity.
GHRH Analog Chemistry
The chemistry of CJC-1295 (no DAC) builds on decades of research into structure activity relationships in GHRH analogs. Early work on GHRH established that the N-terminal 29 amino acids retained essentially full biological activity, while the C-terminal portion of the natural peptide could be removed without significantly affecting receptor binding. This finding made GHRH(1-29) the foundation for most GHRH analog development, including CJC-1295.
The four amino acid substitutions in CJC-1295 are positioned to protect the peptide from cleavage by DPP-IV and from other proteases that contribute to GHRH degradation in research models. The specific substitutions are designed to preserve the alpha helical structure that is important for GHRH receptor binding while making the peptide resistant to enzymatic clearance. These design choices have been the subject of considerable medicinal chemistry research, and they represent one of the more successful examples of stabilizing a small neuropeptide for research applications.
The result of these modifications is a peptide that retains the receptor binding properties of natural GHRH while having a meaningfully extended functional half life in research models. CJC-1295 (no DAC) is generally described in the published literature as producing GH release with kinetics that approximate a stabilized version of endogenous GHRH pulses, rather than the prolonged tonic elevation produced by the with DAC form.
Pulse Kinetics in Animal Research Models
The pulse kinetics of growth hormone release in research animals have been one of the central topics in CJC-1295 (no DAC) research. Endogenous growth hormone is released in pulsatile bursts under the control of GHRH from the hypothalamus, and the pulsatile nature of this release is functionally important for downstream effects on IGF-1 production and target tissue responses. Research interventions that alter GH pulse patterns have been studied for their effects on the broader somatotropic axis in animal models.
CJC-1295 (no DAC) has been characterized for its effects on GH pulse amplitude, pulse duration, and the overall pattern of GH release in research models. The published findings generally support the use of CJC-1295 (no DAC) as a research tool for studying enhanced but still pulsatile GH release, in contrast to the with DAC form which produces sustained tonic elevation. This distinction is functionally important for research design, since the two forms are appropriate for different experimental questions.
In comparative studies, CJC-1295 (no DAC) has been compared with natural GHRH, with sermorelin (another GHRH(1-29) analog), and with other stabilized GHRH derivatives. The general pattern in the literature is that CJC-1295 (no DAC) produces larger and more sustained GH responses than natural GHRH or sermorelin in research models, while still preserving the pulsatile character of release that distinguishes it from the with DAC form.
CJC-1295 With DAC vs CJC-1295 No DAC
The comparison between CJC-1295 with DAC and CJC-1295 no DAC is one of the more important practical distinctions in the published research literature. Both forms share the same underlying GHRH analog sequence with the same four stabilizing substitutions. The only difference is the presence or absence of the DAC modification, but this single chemical difference produces dramatically different pharmacokinetic profiles in research models.
The with DAC form binds to serum albumin through a thioether linkage formed between the maleimido propionic acid group and a cysteine residue on circulating albumin. This covalent attachment to albumin protects the peptide from clearance and produces a half life measured in days. The result is sustained, tonic GH stimulation in research models, which is appropriate for some research questions but not for others.
The no DAC form lacks the maleimide group entirely and therefore does not form the albumin linkage. Its half life is much shorter, and the resulting GH release pattern is pulsatile rather than tonic. For research questions that require approximation of endogenous GH pulse kinetics, the no DAC form is the appropriate tool. For research questions about sustained tonic stimulation, the with DAC form is more appropriate. The choice between the two depends on the specific experimental design rather than on any inherent superiority of one form over the other.
CJC-1295 No DAC and the GHRH Receptor
CJC-1295 (no DAC) acts as an agonist at the GHRH receptor, a G protein coupled receptor expressed on pituitary somatotroph cells. Activation of this receptor in research models triggers the canonical GHRH signaling cascade, which involves coupling to the Gs alpha subunit, activation of adenylyl cyclase, increases in intracellular cyclic AMP, and downstream activation of protein kinase A. This cascade leads to increased growth hormone gene transcription, GH protein synthesis, and release of stored GH from secretory granules.
The receptor binding properties of CJC-1295 (no DAC) have been characterized in radioligand binding studies and in functional assays of GH release from cultured pituitary cells. The published findings support a similar binding affinity to natural GHRH at the GHRH receptor, with the major functional difference being the resistance to proteolytic clearance rather than any change in the receptor interaction itself.
For more on the alternative pathway that contributes to combined GHRH plus GHRP research, see our companion article on Ipamorelin research and selective GHRP ghrelin receptor binding studies.