Tesamorelin vs CJC-1295 (No DAC) vs Ipamorelin on the GH Axis

Two receptors on one cell

The split that matters is the receptor. Anterior pituitary somatotrophs express the growth hormone-releasing hormone receptor (GHRH-R) and the growth hormone secretagogue receptor (GHSR-1a). A ligand at one does not occupy the other.

GHRH-R is a class B G-protein-coupled receptor. Occupancy couples through Gs to adenylyl cyclase and raises cAMP. Mayo cloned a pituitary receptor for growth hormone-releasing hormone and tied that receptor to cAMP signaling (Molecular Endocrinology, 1992).

GHSR-1a couples through Gq to phospholipase C. Phospholipase C generates IP3 and diacylglycerol, and IP3 releases calcium from intracellular stores. Smith and colleagues described secretagogue signaling through a receptor distinct from the GHRH receptor, with phospholipase C in the pathway (Recent Progress in Hormone Research, 1996).

Tesamorelin

Tesamorelin is a synthetic analog of the full 44-residue growth hormone-releasing hormone sequence. The stabilizing change is a trans-3-hexenoyl group on the N-terminus. That cap blocks dipeptidyl peptidase-4 at the position-2 alanine, the cleavage site the unmodified hormone carries.

Identity used across this site: formula C221H366N72O67S, average mass 5,136 Da, CAS 218949-48-5, PubChem CID 16137828. The development code in the literature is TH9507. Research-grade tesamorelin powder is not a finished drug product.

CJC-1295 (No DAC)

CJC-1295 (No DAC), also called modified GRF (1-29), is a 29-residue analog built on the N-terminal fragment of growth hormone-releasing hormone. Wehrenberg and Ling mapped activity across growth hormone-releasing factor fragments (Biochemical and Biophysical Research Communications, 1983). That fragment work is why a 1-29 analog is a research tool. It is not a study of the substituted peptide stocked here.

Relative to native GRF (1-29), the stocked analog carries four substitutions: D-Ala2, Gln8, Ala15, and Leu27. D-Ala2 removes the DPP-4 cleavage site. Gln8 replaces an asparagine that can deamidate. Leu27 replaces methionine, which oxidizes. Identity: formula C152H252N44O42, average mass 3,367.9 Da, CAS 863288-34-0, PubChem CID 91976842.

No DAC means the maleimido-propionic acid group is absent. That group is what lets the other CJC-1295 molecule bind serum albumin. The registry record indexed under the bare name CJC-1295 is the albumin-binding form: PubChem CID 91971820, CAS 446262-90-4, formula C165H269N47O46, average mass 3,647.2 Da. A certificate mass near 3,367.9 Da matches the No DAC peptide. A mass near 3,647.2 Da does not.

Teichman and colleagues studied the albumin-binding form in adults (Journal of Clinical Endocrinology & Metabolism, 2006). That paper is not a record of CJC-1295 (No DAC). This site does not have a primary pharmacokinetic paper for the No DAC peptide, so no exposure time is stated here.

Ipamorelin

Ipamorelin is the pentapeptide Aib-His-D-2-Nal-D-Phe-Lys-NH2. Three residues are not proteinogenic: alpha-aminoisobutyric acid, D-2-naphthylalanine, and D-phenylalanine. Identity: formula C38H49N9O5, average mass 711.9 Da, CAS 170851-70-4, PubChem CID 9831659.

It is a GHSR-1a agonist. The second messenger is the calcium path, not cAMP. Raun and colleagues described ipamorelin as a selective growth hormone secretagogue relative to earlier peptides in that class, including GHRP-2 and GHRP-6, which also moved cortisol and prolactin in the models they tested (European Journal of Endocrinology, 1998). Potency figures from that paper are not reprinted here.

What a pairing changes

CJC-1295 (No DAC) with ipamorelin puts one ligand on GHRH-R and another on GHSR-1a. Tesamorelin with ipamorelin is the same two-receptor layout, with the 44-residue analog in place of the 29-residue fragment. Tesamorelin with CJC-1295 (No DAC) is two ligands at one receptor.

Bowers and colleagues administered a growth hormone-releasing peptide together with growth hormone-releasing hormone (Journal of Clinical Endocrinology & Metabolism, 1990). The compounds in that study are not tesamorelin, CJC-1295 (No DAC), or ipamorelin. The citation supports the two-input design only.

The indexable comparison of tesamorelin and CJC-1295 (No DAC) is the page at /compare/tesamorelin-vs-cjc-1295. CJC-1295 (No DAC) against ipamorelin is /compare/cjc-1295-vs-ipamorelin. Those pages carry the regulatory comparison. This draft stays on sequence, receptor, and second messenger.

Identity comparison

Masses and registry numbers below are the identity figures already used on the compound guides and the indexable comparison pages. They are not assay results from a lot.