CJC 1295
[CAS# 863288-34-0]

Identification

• Classification: Biochemical >> Peptide
• Name: CJC 1295
• Synonyms: L-Tyrosyl-D-alanyl-L-alpha-aspartyl-L-alanyl-L-isoleucyl-L-phenylalanyl-L-threonyl-L-glutaminyl-L-seryl-L-tyrosyl-L-arginyl-L-lysyl-L-valyl-L-leucyl-L-alanyl-L-glutaminyl-L-seryl-L-alanyl-L-arginyl-L-lysyl-L-leucyl-L-leucyl-L-glutaminyl-L-alpha-aspartyl-L-isoleucyl-L-leucyl-L-seryl-L-arginyl-N6-[3-(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)-1-oxopropyl]-L-lysinamide
• Protein Sequence: YADAIFTQSYRKVLAQLSARKLLQDILSR
• Molecular Formula: C₁₅₉H₂₅₈N₄₆O₄₅
• Molecular Weight: 3534.03
• CAS Registry Number: 863288-34-0
• SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](C)NC(=O)[C@H](CC3=CC=C(C=C3)O)N

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Index of refraction: 1.644 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

CJC 1295 is a synthetic peptide developed as an analogue of human growth hormone releasing hormone. The native hypothalamic hormone that stimulates growth hormone secretion from the anterior pituitary has a very short plasma half life because it is rapidly degraded by proteolytic enzymes, particularly dipeptidyl peptidase IV. During the late twentieth century, sustained interest in the physiology of growth hormone secretion and its clinical manipulation led to the search for modified peptides that could resist enzymatic degradation while preserving biological activity. CJC 1295 emerged from this effort as a rationally designed molecule intended to prolong stimulation of growth hormone release after a single administration.

The discovery of CJC 1295 is closely linked to advances in peptide chemistry and endocrine pharmacology in the 1990s and early 2000s. Researchers modified the amino acid sequence of growth hormone releasing hormone to reduce susceptibility to enzymatic cleavage and to enable binding to endogenous plasma proteins. A key innovation was the introduction of a drug affinity complex that allows reversible covalent binding to circulating albumin. This modification markedly extended the circulating half life of the peptide compared with unmodified growth hormone releasing hormone. Preclinical studies demonstrated that the modified peptide retained high affinity for the growth hormone releasing hormone receptor on pituitary somatotrophs and preserved the ability to stimulate cyclic AMP signaling and growth hormone release.

Clinical development focused on evaluating whether prolonged exposure to a growth hormone releasing hormone analogue could safely increase endogenous growth hormone and insulin like growth factor I concentrations. Early human studies showed that a single subcutaneous injection of CJC 1295 produced sustained elevations in circulating growth hormone and insulin like growth factor I lasting several days. Importantly, the pattern of hormone secretion remained pulsatile rather than continuous, reflecting amplification of physiological regulatory mechanisms rather than direct hormone replacement. This characteristic distinguished CJC 1295 from exogenous growth hormone therapy and was considered advantageous in preserving normal feedback control.

Applications of CJC 1295 have primarily been investigated in the context of disorders associated with reduced growth hormone secretion. Clinical trials explored its potential use in adults with growth hormone deficiency and in conditions characterized by age related declines in growth hormone output. The compound was also studied for its effects on body composition, as increases in growth hormone and insulin like growth factor I are associated with changes in fat mass and lean body mass. These studies provided clear evidence that CJC 1295 could produce sustained endocrine effects after infrequent dosing, confirming the success of its design strategy.

Beyond growth hormone deficiency, CJC 1295 contributed more broadly to the understanding of growth hormone releasing hormone analogues as therapeutic agents. Its development demonstrated that extending peptide half life through albumin binding could be an effective approach for modulating endocrine pathways that require pulsatile stimulation. This concept influenced subsequent research into long acting peptide hormones and analogues across multiple therapeutic areas. While CJC 1295 itself has not become a widely approved medication, it occupies an important place in the scientific literature as a proof of principle compound that linked molecular design with physiological hormone regulation.

In summary, CJC 1295 was discovered through targeted modification of growth hormone releasing hormone to overcome rapid degradation and short duration of action. Its application in clinical research established that prolonged yet physiological stimulation of growth hormone secretion is feasible using long acting peptide analogues. The compound has therefore played a significant role in advancing both endocrine pharmacology and peptide drug design, even beyond its immediate investigational use.

References

Melmed S, Kaiser UB, Lopes MB, et al. (2024) Growth hormone releasing hormone and its analogues in health and disease. Nature Reviews Endocrinology 20 12 1–15 DOI: 10.1038/s41574-024-01052-1