Research Overview
CJC-1295 (No DAC) — the GHRH arm
Native GHRH (1-29) is cleaved within minutes by dipeptidyl peptidase-4. CJC-1295 without DAC substitutes four residues — most importantly a D-alanine at position 2 — to block that cleavage while preserving GHRH-receptor affinity. Without the Drug Affinity Complex maleimide that defines the DAC version, the analogue does not bind serum albumin and retains a short duration of action, so it produces a discrete pulse rather than a sustained elevation. That short profile is why the No DAC form is the one usually chosen for studies of pulsatility.
Ipamorelin — the GHS-receptor arm
Why the two are combined
- They act on separate receptors expressed on the same somatotroph, so their effects are not simply redundant.
- GHS-receptor agonism reduces somatostatin tone, which otherwise caps the response to a GHRH analogue.
- Co-administration has been reported to produce a greater measured GH pulse than either peptide alone in animal and cell models.
- Both are short-acting, so the combined signal remains pulsatile rather than continuous — an important distinction in feedback-sensitive systems.
