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CJC-1295 vs ipamorelin: two molecules, two receptors

CJC-1295 and ipamorelin are both described as growth-hormone secretagogues, yet the literature places them at two different receptors.[1],[2]

CJC-1295 is a modified growth-hormone-releasing factor (1-29) built to attach to serum albumin, while ipamorelin is a five-residue peptide from a chemistry series based on growth-hormone-releasing peptides.[3],[4]

This page records how the two differ in structure and receptor pathway and reports no study outcome for either.

Identity side by side

AttributeCJC-1295Ipamorelin
Also recorded as[1],[2]CJC-1295 with DAC; DAC:GRFNNC 26-0161
Structural basis[3],[2]Tetrasubstituted human GRF(1-29) with an added Nε-3-maleimidopropionamide lysine at the C-terminusAib-His-D-2-Nal-D-Phe-Lys-NH2
Length[3],[2]Built on the 29-residue GRF(1-29) chain5 residues
CAS Registry Number[2]Not recorded (unverified for either CJC-1295 form)170851-70-4
Chemical lineage[1],[5],[4]Growth-hormone-releasing hormone analogueSeries lacking the central Ala-Trp dipeptide of GHRP-1
Receptor recorded[1],[2]Growth-hormone-releasing hormone receptorGHRP-type (growth-hormone secretagogue) receptor
Receptor evidence[3],[4]Albumin conjugates activate the GRF receptor on rat anterior pituitaryGHRP and GHRH antagonist profiling pointed to a GHRP-like receptor
Serum albumin attachment[3],[2]Maleimide group designed to react with albumin cysteine 34None recorded

How do the two structures differ?

CJC-1295 starts from the first 29 residues of human growth-hormone-releasing factor, carries four substitutions, and adds a lysine bearing a 3-maleimidopropionamide group at the C-terminus.[3]

That maleimide is meant to react with the free thiol on cysteine 34 of serum albumin, and in rat plasma a CJC-1295-immunoreactive species was found on the albumin band.[3]

Ipamorelin is far smaller and includes three non-standard building blocks: 2-aminoisobutyric acid, D-2-naphthylalanine and D-phenylalanine.[2]

It came out of a growth-hormone-releasing peptide chemistry programme, from a series of compounds lacking the central Ala-Trp dipeptide of GHRP-1.[4]

Which receptor does each act through?

The GHRH receptor was cloned from pituitary in 1992 as a seven-transmembrane receptor related to the secretin and vasoactive intestinal peptide receptors.[6]

Albumin conjugates of the CJC-1295 series were reported to activate this GRF receptor on the anterior pituitary in rats.[3]

Ipamorelin's growth-hormone-releasing activity was traced, using GHRP and GHRH antagonists, to a GHRP-like receptor and not to the GHRH receptor.[4]

A G protein-coupled receptor of pituitary and hypothalamus that is the target of the growth-hormone secretagogue class was cloned in 1996, and the library records ipamorelin's target as this GHRP-type receptor.[7],[2]

What does the literature not compare?

No publication cited here studied CJC-1295 and ipamorelin in the same experiment.[3],[5],[4]

The published figures for each compound come from different species, designs and endpoints, and none is set against the other on this page.[5],[4],[8]

Limitations

A shared label such as growth-hormone secretagogue groups molecules by one downstream hormone; the receptor records show the two do not share an entry point.[1],[2]

The CJC-1295 receptor and albumin findings come from rat tissue and rat plasma, and ipamorelin's receptor profiling comes from rat cells and animals.[3],[4]

Compound profiles

References

  1. CJC-1295 research profile, PepGenex Science (identity and records, with their sources).
  2. Ipamorelin research profile, PepGenex Science (identity and records, with their sources).
  3. 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. PMID 15817669 · DOI 10.1210/en.2004-1286
  4. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561. PMID 9849822 · DOI 10.1530/eje.0.1390552
  5. Teichman SL, Neale A, Lawrence B, et al. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805. PMID 16352683 · DOI 10.1210/jc.2005-1536
  6. Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol. 1992;6(10):1734-1744. PMID 1333056 · DOI 10.1210/mend.6.10.1333056
  7. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974-977. PMID 8688086 · DOI 10.1126/science.273.5277.974
  8. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Title withheld on this site (see the publication record). International Journal of Colorectal Disease 2014. PMID 25331030 · DOI 10.1007/s00384-014-2030-8