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

This study published in Endocrinology described the discovery and pharmacological characterization of CJC-1295 as a long-lasting analog of human GH-releasing factor (hGRF). The research, conducted by the Canadian company ConjuChem, focused on developing albumin bioconjugation technology to extend the half-life of therapeutic peptides.

The approach involved chemically modifying hGRF(1-29) — the biologically active fragment of GHRH — with a reactive maleimidopropionic acid group that covalently binds to serum albumin in vivo. This binding occurs spontaneously after subcutaneous injection, effectively "shielding" the peptide from enzymatic degradation and dramatically increasing its half-life from minutes to days.

In rats, CJC-1295 demonstrated a 4-fold increase in the area under the curve (AUC) of GH over 2 hours compared to native hGRF(1-29). Furthermore, bioconjugation did not compromise biological activity: CJC-1295 retained full affinity for the GHRH receptor in the anterior pituitary, confirmed by in vitro binding and cell stimulation assays.

This work was pivotal in identifying and validating CJC-1295 as a clinical candidate, paving the way for the human trials that followed. The DAC (Drug Affinity Complex) technology demonstrated in this study influenced the development of other long-acting peptides in the pharmaceutical industry. Interestingly, the version without DAC (Mod GRF 1-29) also became widely used in research, with an intermediate half-life and the advantage of more physiological GH pulses.