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CJC-1295 with DAC Research Standard
CJC-1295 with DAC (CAS 446262-90-4) is the compound the original identification paper actually calls CJC-1295: a tetrasubstituted form of hGRF(1-29) carrying an added Nε-3-maleimidopropionamide derivative of lysine at the C terminus. That maleimide is the Drug Affinity Complex, and it is the whole point of the molecule.[1]
Mechanism of Action & Research Context
The molecular target is the growth hormone-releasing hormone receptor (GHRH-R), a class II GPCR on pituitary somatotrophs — a different receptor from the GHS-R1a targeted by the ghrelin-mimetic secretagogues.
How the DAC works. The maleimide reacts with the free thiol on Cys34 of serum albumin, forming a covalent bioconjugate in circulation. Western blot of plasma from a treated rat showed CJC-1295 immunoreactivity on the band corresponding to serum albumin, appearing within 15 minutes and still present beyond 24 hours.[1]
What that buys. Compared with unconjugated hGRF(1-29), CJC-1295 produced a fourfold increase in GH area under the curve over two hours, and the compound remained detectable in plasma beyond 72 hours. The albumin conjugates also showed enhanced in vitro stability against DPP-IV and were bioactive in a GH secretion assay in cultured rat anterior pituitary cells.[1]
DPP-IV is the limiting factor. GRF(1-29)NH2 is degraded mainly by dipeptidyl peptidase IV, which clips the N-terminal dipeptide to leave inactive GRF(3-29)NH2. Analogues designed to resist plasma DPP-IV are markedly more stable, and that resistance carries across compartments — a DPP-IV-resistant analogue was far more stable than the parent in intestinal enterocytes as well as plasma.[2]
The receptor. GHRH-R is a class II G-protein-coupled receptor required for normal growth hormone synthesis and release, and for normal growth and proliferation of pituitary somatotrophs. Mutations in mouse and human are associated with GH deficiency, short stature and pituitary hypoplasia. Alternative mRNA splicing produces variants proposed to act as dominant-negative inhibitors of the wild-type receptor.[3]
A larger molecule, by design. Its formula C165H269N47O46 exceeds the No-DAC analogue’s C152H252N44O42 by exactly the added maleimidopropionamide-lysine. The two are not interchangeable and should not share a CAS number.
Research Applications
Primary fields of in vitro and preclinical laboratory investigation include:
Bioconjugation chemistry at the albumin Cys34 thiol, including conjugate formation kinetics.[1]
Extended-exposure pharmacokinetics in preclinical models.[1]
GH secretion assays in cultured anterior pituitary cells.[1]
Comparative work against unmodified GRF(1-29) and the No-DAC analogue.[1,2]
Analytical Documentation
Purity and identity vary by manufacturing lot. Kimera Chems does not publish a single fixed purity figure for this item; refer to the batch-specific Certificate of Analysis (COA) issued for the lot received, which reflects third-party analytical testing for that lot.
References
- Jetté L, Léger R, Thibaudeau K, 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;146(7):3052–3058. doi:10.1210/en.2004-1286
- Bai JP, Chang LL. The involvement of dipeptidyl peptidase IV in brush-border degradation of GRF(1-29)NH2 by intestinal mucosal cells. J Pharm Pharmacol. 1995;47(8):698–701. doi:10.1111/j.2042-7158.1995.tb05863.x
- Gaylinn BD. Growth hormone releasing hormone receptor. Recept Channels. 2002;8(3–4):155–162. PMID: 12529933.
