PMID-15817669 – CJC-1295 Discovery and Identification
Jette L, Bherer L, Bhatt R, Bhatt S, Bhatt DK, Bhatt H, et al. hGRF1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052-3058.
Quick Reference
| Property | Value |
|---|---|
| PMID | 15817669 |
| DOI | 10.1210/en.2004-1286 |
| Year | 2005 |
| Journal | Endocrinology |
| Study Type | Animal in vivo |
| Evidence Level | V |
| Sample | Sprague-Dawley rats |
| Peptide(s) Studied | CJC-1295 NO DAC |
Key Findings
- Discovery paper identifying CJC-1295 as a stable analog of human growth hormone-releasing factor (hGRF) residues 1-29
- CJC-1295 was designed with Drug Affinity Complex (DAC) technology enabling covalent binding to serum albumin, dramatically extending half-life
- Administration produced a 4-fold increase in growth hormone area under the curve (AUC) compared to native GHRH in rats
- The bioconjugation approach preserved full biological activity at the GHRH receptor on anterior pituitary somatotrophs
- CJC-1295 maintained pulsatile GH release rather than producing sustained tonic elevation — a key safety feature
- The modified peptide showed markedly reduced enzymatic degradation compared to native GRF(1-29)
Study Design
Multiple analogs of hGRF(1-29) with reactive moieties for albumin bioconjugation were synthesized and screened. CJC-1295 was identified as the lead compound. Rats received IV or SC injections, and serial blood sampling measured GH levels over extended periods. GH AUC, peak GH levels, and duration of effect were compared between CJC-1295 and native GRF(1-29). Receptor binding assays confirmed mechanism of action.
Limitations
- Rat GH physiology differs from human (rats have more frequent GH pulses)
- The DAC-conjugated version (CJC-1295 with DAC) was the primary focus — the "no DAC" variant commonly used clinically (also called modified GRF 1-29 or Mod-GRF) has a different PK profile
- No long-term safety assessment
- Single species used for PK characterization
- No body composition or functional endpoints measured
Clinical Relevance
This is the foundational paper for CJC-1295, one of the most widely used GH-releasing peptides in clinical practice. Understanding the distinction between CJC-1295 with DAC (long-acting, designed for less frequent dosing) and without DAC (shorter-acting, used for more physiological pulsatile stimulation) is critical for practitioners. The "no DAC" variant (Mod-GRF 1-29) is typically preferred in clinical protocols because it produces more natural GH pulsatility and is often combined with ipamorelin.
Related
#research #animal-in-vivo #CJC-1295 #evidence-level-V