CJC-1295

What is CJC-1295?

CJC-1295 is a modified GHRH peptide developed by the Canadian biotechnology company ConjuChem. Native GHRH has a half-life measured in minutes because it is rapidly cleaved by DPP-4 at the second amino acid position. ConjuChem addressed this by substituting the vulnerable amino acids and attaching a reactive maleimide group, called the Drug Affinity Complex or DAC, to the peptide's C-terminus.

Once injected, the maleimide group reacts spontaneously with a free cysteine residue on serum albumin. Because albumin is the most abundant plasma protein and has a long circulating half-life, this covalent linkage effectively extends the functional half-life of CJC-1295 from minutes to days or longer. The same DAC technology was explored by ConjuChem for other therapeutic applications.

A commonly encountered variation in research communities, labeled Modified GRF 1-29 or Mod GRF 1-29, lacks the DAC modification and is chemically distinct from CJC-1295. The two should not be treated as interchangeable, though both are based on the GHRH 1-29 sequence.

Mechanism of action

CJC-1295 activates the GHRH receptor on pituitary somatotrophs, the same receptor as endogenous GHRH and the approved drug tesamorelin. Receptor activation triggers release of stored growth hormone from the pituitary gland, which in turn stimulates production of insulin-like growth factor 1 (IGF-1) from the liver.

Because the DAC modification gives CJC-1295 a prolonged presence in circulation, it produces a sustained rather than pulsatile stimulus on the GHRH receptor. This contrasts with the normal pulsatile pattern of endogenous GHRH and with shorter-acting GHRH analogs. Whether a sustained versus pulsatile stimulus produces meaningfully different downstream effects is an active area of research discussion.

• •Binds the pituitary GHRH receptor, stimulating release of stored growth hormone
• •Growth hormone in turn drives hepatic production of IGF-1
• •DAC modification produces prolonged circulation via covalent albumin binding
• •Prolonged GHRH receptor stimulus may alter the normal pulsatile pattern of GH secretion

Clinical trial history

A phase 1 and 2 dose-escalation study of CJC-1295 in healthy adults was conducted by ConjuChem and published by Teichman and colleagues in the Journal of Clinical Endocrinology and Metabolism in 2006. The study reported dose-dependent increases in plasma growth hormone and IGF-1 concentrations following single and multiple subcutaneous doses, with effects persisting for several days after a single injection, consistent with the albumin binding mechanism.

Clinical development of CJC-1295 did not advance beyond these early-phase studies. ConjuChem explored the DAC platform more broadly but did not pursue regulatory approval for CJC-1295 as a standalone therapeutic. No phase 3 trials of CJC-1295 have been published.

Safety and regulatory context

CJC-1295 is not approved by the FDA or any other regulatory agency for any indication. The early-phase study by Teichman et al. reported it was generally well tolerated in the doses tested, with injection site reactions and water retention among the noted observations, but the safety database from controlled trials is limited.

The World Anti-Doping Agency prohibits growth hormone-releasing hormone and its analogs under section S2 of the Prohibited List at all times. Athletes subject to WADA rules face anti-doping consequences for the use of CJC-1295.

Material sold as research CJC-1295 is unregulated. Purity, identity, and the presence or absence of the DAC modification cannot be verified without independent analytical testing. It is intended strictly for laboratory use and is not cleared for human administration.

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