CJC-1295 (without DAC) vs IGF-1 LR3 (Long R3 IGF-1)

CJC-1295 (without DAC)

CJC-1295 without DAC, also called modified GRF (1-29), is a 29-residue synthetic analogue of growth hormone-releasing hormone (GHRH). Native GHRH has 44 residues, but its first 29 carry the receptor-binding activity, and this peptide is built on that shortened sequence with four amino-acid substitutions intended to slow breakdown. The name causes confusion: CJC-1295 originally referred to a version carrying a drug affinity complex (DAC), a reactive linker that binds albumin and greatly prolongs circulation. The form described here lacks that linker. Human studies of the DAC version exist but are few; published work on the form without DAC is thinner still, and much of what is said about it is inferred from the parent hormone.

IGF-1 LR3 (Long R3 IGF-1)

IGF-1 LR3 is an 83-residue analogue of insulin-like growth factor 1, with an N-terminal extension and arginine replacing glutamate at position 3. The extension adds 13 amino acids to the 70 of native IGF-1, and the name records both changes: L for long, R3 for the arginine. Together the modifications lower its affinity for the IGF-binding proteins that normally hold most IGF-1 in bound complexes. It is produced recombinantly and is used as a supplement in serum-free media for growing mammalian cell lines. Outside cell culture, published work consists mainly of animal studies, and human data are very limited.

How CJC-1295 (without DAC) acts

Like native GHRH, the peptide has been reported to bind the GHRH receptor, a class B G protein-coupled receptor on somatotroph cells of the anterior pituitary. Receptor activation couples to Gs, raising intracellular cAMP and releasing stored growth hormone; circulating growth hormone in turn drives IGF-1 production, mainly in the liver. The substitutions, D-alanine at position 2, glutamine at 8, alanine at 15 and leucine at 27, were chosen to resist cleavage by dipeptidyl peptidase-4 and to reduce deamidation and oxidation at vulnerable residues. Without the albumin-binding linker its half-life is short, and pharmacokinetic data specific to this form are sparse.

How IGF-1 LR3 (Long R3 IGF-1) acts

IGF-1 LR3 is reported to activate the type 1 IGF receptor, a receptor tyrosine kinase, with an affinity similar to or somewhat lower than that of native IGF-1. Its defining property is weak binding to the IGF-binding proteins, which in serum and conditioned culture media normally sequester most IGF-1. With less of it held in complexes, more is free to reach the receptor, which is the usual explanation for its higher apparent activity in cell culture. Receptor activation engages insulin receptor substrate proteins and the PI3K–Akt–mTOR and Ras–MAPK pathways, which govern protein synthesis, proliferation and survival in the cell types studied.

The records side by side

• Type: CJC-1295 (without DAC), GHRH analog (Modified GRF 1-29); IGF-1 LR3 (Long R3 IGF-1), Modified IGF-1 analog
• Molecular weight: CJC-1295 (without DAC), 3647.2 g/mol; IGF-1 LR3 (Long R3 IGF-1), not recorded
• Molecular formula: CJC-1295 (without DAC), C165H269N47O46; IGF-1 LR3 (Long R3 IGF-1), not recorded

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.