CJC-1295 no DAC is a synthetic analog of GHRH(1-29), which is usually classified as tetrasubstituted variants of GRF 1-29 without the albumin-binding DAC complex. It is important that there is confusion in the names in the literature and on the market: the FDA separately identifies CJC-1295 free base and CJC-1295 DAC as different active forms. For no DAC, a 29-amino acid sequence with substitutions at positions 2, 8, 15 and 27 is indicated, and its molecular weight is 3367.95 g/mol.  December 4, 2024 Pharmacy Compounding Advisory Committee (PCAC) Meeting

Growth Hormone stimulation
The main research area of CJC-1295 no DAC is related to the stimulation of the GHRH receptor in the pituitary gland and increased endogenous secretion of growth hormone. Unlike the DAC version, this form does not contain a C-terminal albumin binding group, so it acts noticeably shorter and is usually considered a more "pulse" form of the GHRH analog. The very principle of creating such analogues is based on increasing resistance to enzymatic degradation while maintaining agonistic activity against the GHRH receptor.  December 4, 2024 Pharmacy Compounding Advisory Committee (PCAC) Meeting

Short action and no DAC
The key difference between CJC-1295 no DAC and CJC-1295 DAC is that no DAC does not have a maleimidopropionamide-lysine fragment, due to which the DAC version binds to serum albumin and circulates much longer. The DAC form has been shown to be present in plasma for more than 72 hours and have a multi-day pharmacological effect, whereas no DAC is considered precisely as a short-acting form unmodified by this mechanism. Therefore, in research, it is usually contrasted with the prolonged DAC variant.  Human Growth Hormone-Releasing Factor (hGRF)1–29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog | Endocrinology | Oxford Academic

Structural modifications and stability
CJC-1295 no DAC is of interest due to amino acid substitutions aimed at increasing the resistance of the molecule to enzymatic degradation. The sequence is specified in the FDA memo for free base 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. Some early studies of GHRH analogues showed that even replacing Ala at position 2 with D-Ala already reduces metabolic clearance and increases the half-life compared to the initial GHRH(1-29)-NH2, and further modifications were created specifically to enhance this resistance.  December 4, 2024 Pharmacy Compounding Advisory Committee (PCAC) Meeting

Studies of metabolism and body composition
Like other GHRH analogues, CJC-1295 no DAC is being studied in the context of regulation of the GH/IGF-1 axis, protein metabolism, lipid metabolism, and age-related decline in somatotropic function. Here, the interest in the molecule is related not so much to a prolonged increase in IGF-1, as in the DAC version, but rather to the possibility of studying a more short-term and physiologically similar stimulation of GH secretion. This makes no DAC in demand in research schemes, where a short response without prolonged albumin-dependent exposure is important. This is a conclusion based on the mechanism of action and the differences between the forms, and not the direct result of a separate large clinical trial specifically for no DAC.  December 4, 2024 Pharmacy Compounding Advisory Committee (PCAC) Meeting

Pharmacokinetic interest
The CJC-1295 no DAC is valuable as a model of a short-range GHRH analog. For related short GHRH analogues, clinical studies have shown that structural substitutions reduce clearance and prolong action compared with native GHRH(1-29), but without reaching the multi-day pharmacokinetics of the DAC version. Therefore, no DAC is usually considered as a form for more frequent administration and a shorter window of activity, whereas DAC is intended for prolonged stimulation.  Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men - PubMed

Links
 1. U.S. Food and Drug Administration. December 4, 2024 Pharmacy Compounding Advisory Committee Meeting. Section on CJC-1295 free base and CJC-1295 DAC. December 4, 2024 Pharmacy Compounding Advisory Committee (PCAC) Meeting
 2. Jetté, L. et al. Human Growth Hormone-Releasing Factor (hGRF)1–29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog. Endocrinology, 2005.  Human Growth Hormone-Releasing Factor (hGRF)1–29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog | Endocrinology | Oxford Academic
 3. Soule, S. et al. 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.  Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men - PubMed
 4. Schally, A. V. et al. The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders. 2024. The development of growth hormone-releasing hormone analogs: Therapeutic advances in cancer, regenerative medicine, and metabolic disorders - PMC