KEIFEI Growth Hormone - Releasing Hormone CJC 1295 2mg x 10 vial

KEIFEI CJC-1295

Presentation: Each 2ml multidose vial contains 2 mg/vial. Orange colour cap with KeiFei wording stamp on it. CJC-1295 is a Long-acting
growth-hormone-releasing hormone (GHRH) analog. Because of the long half-life and stability of the CJC-1295 analog, it appears to
become more and more popular.

CJC-1295 is a Long acting GHRH analog. Growth-hormone-releasing hormone (GHRH), also known as growth-hormone-releasing factor
(GRF or GHRF) or somatocrinin, is a 44-amino acid peptide hormone produced in the hypothalamus by the arcuate nucleus. GHRH
stimulates growth hormone (GH) secretion from the pituitary. GHRH is released in a pulsatile manner, stimulating pulsatile release of GH
respectively.
In addition, GHRH also promotes slow-wave sleep.

The active portion of this GRF or GHRH peptide can be found as a 29 amino acid long peptide and is appropriately named GHRH1-29. This
pulsatile release of various peptides is due to the negative feedback loop that is part of the hGH axis and controls the amount of hGH that
your body produces to keep it in a homeostatic environment. Despite the effectiveness of GHRH to stimulate growth hormone release there
are a number of problems associated with using it in vivo. The most noteworthy problem is the half life of the peptide, which has been
shown to be ~7 minutes using advanced HPLC technologies that have proven to be very accurate. The reason for this relatively short half
life is due to an enzyme called dipeptidylaminopeptidase IV (DPP-IV), which has a high affinity for the amino acids Ala and Pro and in the
case of GHRH it cleaves the 1 and 2 positions that consist of Tyr-Ala, creating GHRH3-29, an inactive form of the peptide. To prevent the
problems associated with natural GHRH, pharmaceutical companies looked at new ways to increase the half life and bioavailability of
these smaller peptides with technologies that work far different than other technologies, such as PEGylation.

CJC-1295 is a synthetic modification of growth hormone releasing factor (GRF) with D-Ala, Gln, Ala, and Leu substitutions at positions 2, 8,
15, and 27 respectively. These substitutions create a much more stable peptide with the substitution at position 2 to prevent DPP-IV
cleavage, position 8 to reduce asparagine rearrangement or amide hydrolysis to aspartic acid, position 15 to enhance bioactivity, and
position 27 to prevent methionine oxidation. By applying the Drug Affinity Complex (DAC) technology to GRF, the peptide selectively and
covalently binds to circulating albumin after subcutaneous (SC) administration, thus prolonging its half-life. These substitutions are key in
increasing the overall half life of CJC-1295 but there lies an even greater reason as to why the half life has been extended from ~7
minutes to greater than 7 days! Bioconjugation is a relatively newer technology that takes a reactive group and attaches it to a peptide,
which in turn reacts with a nucleophilic (usually a partially negative molecule) entity found in the blood to form a more stable bond.

Albumin, one of the most abundant substances in the human body is chosen as the nucelophile by this particular peptide thanks to a
Cys34 thiol group that attracts it. By combining the tetrasubstituted GHRH analogue with maleimodoproprionic acid using a Lys linker,
you create a GHRH peptide with a high binding affinity for albumin. Once the CJC-1295 molecule has attached itself to albumin, it is given
an extended half life and bioavailability thanks to the albumin preventing enzymatic degredation and kidney excretion. In fact,
bioconjugation is so effective that there was less than 1% of CJC-1295 left unreacted in vivo and over 90% was stabilized after
subcutaneous injection. This means that you get more of what you paid for working for you. There was no DPP-IV degredation observed on
CJC -1295 in any of the various experiments conducted.