This is a working overview of GHRH analogue, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2025-10-16. Anything still debated is marked as such rather than presented as settled.
The drug affinity complex is a maleimidopropionic acid group attached to a lysine side chain. It reacts with the free thiol of cysteine-34 on circulating albumin, forming a covalent bond. This conjugation keeps the peptide in the bloodstream and shields it from rapid renal filtration and proteolysis. Reported circulation half-lives for the albumin-bound form fall in the range of roughly six to nine days in early human studies.
Binding to GHRH receptors on pituitary somatotroph cells triggers cyclic AMP signaling and stimulates growth hormone synthesis and release. Because the peptide acts upstream of the pituitary, effects are mediated through endogenous growth hormone rather than direct receptor activation in peripheral tissues. Increases in insulin-like growth factor 1 are generally described as a downstream consequence. Most published human exposure data come from small early-stage studies, and the clinical significance of the pharmacokinetic profile remains incompletely characterized.
CJC-1295 is a synthetic analogue of growth hormone-releasing hormone, built on the 29-amino-acid GHRH(1-29) fragment. Four substitutions distinguish it from the natural sequence: D-alanine at position 2, glutamine at position 8, alanine at position 15, and leucine at position 27. These changes reduce enzymatic cleavage and extend the peptide's persistence in circulation. The compound is discussed in two forms, one carrying a drug affinity complex and one without it.
CJC-1295 belongs to a family of synthetic peptides modeled on growth hormone-releasing hormone, the hypothalamic signal that prompts the pituitary to release growth hormone. The compound is built from the first twenty-nine amino acids of the natural human sequence, a fragment that retains full receptor binding capacity. Native growth hormone-releasing hormone is degraded quickly in circulation, so the fragment alone has limited practical value. Early work therefore focused on chemical modifications that preserve receptor binding while slowing enzymatic breakdown. The result is a molecule described in the literature as a long-acting analog of the natural hormone.
Two forms circulate under the CJC-1295 name, and they differ by a single appended group. The version without a drug affinity complex carries four substitutions along the peptide chain, including a D-alanine near the amino terminus and replacements at three other positions. These changes block the enzyme dipeptidyl peptidase IV and remove a methionine residue that is prone to oxidation. The modified fragment is frequently labeled MOD GRF 1-29. Naming conventions are inconsistent across informal sources, which is a common source of confusion.
The second form adds a maleimide-bearing linker to the lysine at the carboxyl end. This group reacts with cysteine-34 on circulating serum albumin, forming a covalent bond that keeps the peptide in the bloodstream for far longer. ConjuChem developed the molecule as a way to extend the action of a peptide without frequent administration. The albumin attachment is the defining structural feature of the drug affinity complex version. Whether continuous exposure produces effects distinct from shorter pulses remains an unresolved research question.
| Property | Value | Notes |
|---|---|---|
| Physical form | Lyophilized white powder | Supplied as a freeze-dried solid for research use |
| Molecular weight | Approximately 3,647 Da (DAC form) | Lower for the variant lacking the albumin-binding moiety |
| Solubility | Soluble in water and aqueous buffer | Typically dissolved in sterile or bacteriostatic water |
| Typical storage temperature | −20 °C or below | Dry powder, desiccated and protected from light |
| Common analytical method | Reversed-phase HPLC with mass spectrometry | Used for purity estimation and identity confirmation |
Two related forms appear under the CJC-1295 name. The simpler analogue, commonly written as modified GRF(1-29), carries the four substitutions but no additional conjugation. The second form attaches a maleimidopropionic acid linker to a lysine residue, a modification frequently called the drug affinity complex. That linker reacts with the free thiol on serum albumin to form a covalent bond. Because albumin has a long residence time in blood, the conjugated peptide stays in circulation far longer than the unconjugated analogue.
Receptor level activity follows the canonical GHRH pathway. The peptide binds the GHRH receptor, a class B G protein coupled receptor on somatotroph cells of the anterior pituitary. Binding raises intracellular cyclic AMP, which promotes calcium entry and the release of growth hormone into the bloodstream. Because the molecule acts at the same receptor as the endogenous hormone, its effect is superimposed on the natural pulsatile rhythm rather than replacing it. Whether sustained receptor occupation leads to desensitization is not fully settled.
At the pituitary, the peptide binds the growth hormone-releasing hormone receptor on somatotroph cells. Receptor activation raises intracellular cyclic AMP and triggers release of stored growth hormone. Somatostatin and other hypothalamic signals modulate this response. Negative feedback from insulin-like growth factor 1 also influences output. The same regulatory architecture operates with the native hormone. Whether the synthetic analog alters feedback dynamics over repeated exposure remains an open question. Most published receptor work uses cell models rather than intact human systems.
CJC-1295 is a synthetic peptide belonging to the growth hormone-releasing hormone analog family. It comprises twenty-nine amino acid residues derived from the N-terminal region of natural GHRH. The molecule incorporates several non-natural substitutions that increase resistance to enzymatic degradation. These modifications extend its activity compared with the native hormone fragment. Researchers use it to study pituitary growth hormone secretion in laboratory and clinical settings. This compound is distinct from native GHRH in its stability profile.
The peptide backbone includes a D-alanine at position two, which resists cleavage by dipeptidyl peptidase IV, and several other substitutions that reduce degradation. Its molecular weight is roughly 3.4 kDa without the linker and about 3.6 kDa with it. The molecule is water soluble and is normally supplied as a lyophilized powder. Precise sequence and mass values depend on which variant is described, so technical documents usually state the exact form being referenced.
CJC-1295 is a synthetic peptide designed as a long-acting analogue of growth hormone-releasing hormone (GHRH). Its structure derives from the first 29 amino acids of native GHRH, a fragment often called GRF(1-29). Four substitutions were introduced to slow enzymatic breakdown and extend activity relative to the natural sequence. The compound was developed by ConjuChem as part of a broader effort to improve the pharmacokinetic profile of peptide hormones. It is studied in laboratory and clinical research settings rather than appearing as a naturally occurring substance.
Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and the hydrophobic effect. Many are physical contacts with molecular associations between chains that occur in a cell or in a living organism in a specific biomolecular context. Proteins rarely act alone as their functions tend to be regulated. Many molecular processes within a cell are carried out by molecular machines that are built from numerous protein components organized by their PPIs. These physiological interactions make up the so-called interactomics of the organism, while aberrant PPIs are the basis of multiple aggregation-related diseases, such as Creutzfeldt–Jakob and Alzheimer's diseases. PPIs have been studied with many methods and from different perspectives: biochemistry, quantum chemistry, molecular dynamics, signal transduction, among others. All this information enables the creation of large protein interaction networks – similar to metabolic or genetic/epigenetic networks – that empower the current knowledge on biochemical cascades and molecular etiology of disease, as well as the discovery of putative protein targets of therapeutic interest.
=== brGDGT === The building blocks of brGDGT, specifically the long alkyl groups (iso-diabolic acid), are detected in acidobacteria subdivisions 1, 3, 4, and 6. Small amounts of brGDGT-I was detected in Acidobacteriaceae strain A2-4c by full mass spectrum and tentatively in Acidobacteriaceae strain 307 by single-ion monitoring MS; none has been detected in the 44 other strains tested as of 2018. More complex brGDGTs known from nature have not yet been detected in any cell culture.
The majority of serpin diseases are due to protein aggregation and are termed "serpinopathies". Serpins are vulnerable to disease-causing mutations that promote formation of misfolded polymers due to their inherently unstable structures. Well-characterised serpinopathies include α1-antitrypsin deficiency (alpha-1), which may cause familial emphysema, and sometimes liver cirrhosis, certain familial forms of thrombosis related to antithrombin deficiency, types 1 and 2 hereditary angioedema (HAE) related to deficiency of C1-inhibitor, and familial encephalopathy with neuroserpin inclusion bodies (FENIB; a rare type of dementia caused by neuroserpin polymerisation). Each monomer of the serpin aggregate exists in the inactive, relaxed conformation (with the RCL inserted into the A-sheet). The polymers are therefore hyperstable to temperature and unable to inhibit proteases. Serpinopathies therefore cause pathologies similarly to other proteopathies (e.g. prion diseases) via two main mechanisms. First, the lack of active serpin results in uncontrolled protease activity and tissue destruction. Second, the hyperstable polymers themselves clog up the endoplasmic reticulum of cells that synthesize serpins, eventually resulting in cell death and tissue damage. In the case of antitrypsin deficiency, antitrypsin polymers cause the death of liver cells, sometimes resulting in liver damage and cirrhosis. Within the cell, serpin polymers are slowly removed via degradation in the endoplasmic reticulum.
However, although (R)-MDMA partially substitutes for lysergic acid diethylamide (LSD) in animal drug discrimination tests, it did not produce the head-twitch response, a behavioral proxy of psychedelic effects, at any tested dose. In any case, findings in this area are conflicting. (R)-MDMA is inactive as an agonist of the human TAAR1, whereas (S)-MDMA shows very weak potency as an agonist of the receptor (EC50Tooltip half-maximal effective concentration = 74,000 nM). MDMA is a well-known serotonergic neurotoxin and this has been demonstrated both in animals and in humans. There is evidence that the serotonergic neurotoxicity of MDMA may be driven primarily by (S)-MDMA rather than (R)-MDMA. (R)-MDMA shows substantially lower or potentially no neurotoxicity compared to (S)-MDMA in animal studies. This has been the case even when doses of (R)-MDMA were increased to account for its lower potency than (S)-MDMA. However, more research is needed to confirm this in other species, such as non-human primates. In contrast to (S)-MDMA, (R)-MDMA does not produce hyperthermia in rodents, and this may be involved in its reduced risk of neurotoxicity, as hyperthermia augments and is essential for the serotonergic neurotoxicity of MDMA. The reduced potency of (R)-MDMA as a dopamine releasing agent may also be involved in its reduced neurotoxic potential, as dopamine release is likewise essential for the neurotoxicity of MDMA. The hyperthermia of MDMA may in fact be mediated by dopamine release.
=== Supersecondary structure === Tertiary protein structures can have multiple secondary elements on the same polypeptide chain. The supersecondary structure refers to a specific combination of secondary structure elements, such as β-α-β units or a helix-turn-helix motif. Some of them may be also referred to as structural motifs.
Sources: en.wikipedia.org
=== Atom-based === Standard approaches of this type, using atomic contributions, have been named by those formulating them with a prefix letter: AlogP, XlogP, MlogP, etc. A conventional method for predicting log P through this type of method is to parameterize the distribution coefficient contributions of various atoms to the overall molecular partition coefficient, which produces a parametric model. This parametric model can be estimated using constrained least-squares estimation, using a training set of compounds with experimentally measured partition coefficients. In order to get reasonable correlations, the most common elements contained in drugs (hydrogen, carbon, oxygen, sulfur, nitrogen, and halogens) are divided into several different atom types depending on the environment of the atom within the molecule. While this method is generally the least accurate, the advantage is that it is the most general, being able to provide at least a rough estimate for a wide variety of molecules.
The ionic radius is expected to decrease regularly for Mn2+ to Zn2+. This would be the normal periodic trend and would account for the general increase in stability. The crystal field stabilisation energy (CFSE) increases from zero for manganese(II) to a maximum at nickel(II). This makes the complexes increasingly stable. CFSE returns to zero for zinc(II). Although the CFSE for copper(II) is less than for nickel(II), octahedral copper(II) complexes are subject to the Jahn–Teller effect which results in a complex having extra stability. Another example of the effect of ionic radius the steady increase in stability of complexes with a given ligand along the series of trivalent lanthanide ions, an effect of the well-known lanthanide contraction.
== Derived units and SI multiples == The only SI derived unit with a special name derived from the mole is the katal, defined as one mole per second of catalytic activity. Like other SI units, the mole can also be modified by adding a metric prefix that multiplies it by a power of 10:
== Politics == Manmohan Singh (1933–2024), former Prime Minister of India from 2004 to 2014 Ajit Pal Singh Kohli, Indian politician and MLA from Patiala Assembly constituency Amolak Rattan Kohli (born 1942), former governor of the Indian state of Mizoram from 2001 to 2006 Om Prakash Kohli (1935–2023), former governor of the Indian state of Gujarat from 2014 to 2019 Abdul Ghani Kohli (born 1943), Indian J&K politician Mohammad Aslam Kohli, Indian J&K politician Krishna Kohli (born 1979), Pakistani politician (While her name is spelled as Kohli, she originates from the Koli people, who are unrelated to the Kohlis of the Khukhrain clan) Kuli Kohli (born 1970), Indian-British poet, writer, disabled activist and local council member Veeru Kohli (1964–2023), Pakistani human rights activist (While her name is spelled as Kohli, she originates from the Koli people, who are unrelated to the Kohlis of the Khukhrain clan)
Sources: en.wikipedia.org
The two share the same 29-amino-acid backbone. CJC-1295 carries an additional albumin-binding moiety that markedly extends its residence time in circulation, while the form without that moiety clears faster. Literature sometimes applies the name loosely to either variant.
It has not been approved by major regulatory agencies for any therapeutic indication. Material sold under this name is typically distributed for laboratory research only. Clinical use is not supported by large controlled trials.
Early human studies of the albumin-binding form reported circulation half-lives on the order of several days. The value depends on assay method and study design. Estimates for the form without the binding moiety are considerably shorter.
The names are often used interchangeably in casual writing, but they are not strictly identical. Modified GRF(1-29) refers to the unconjugated analogue carrying only the four substitutions. The version sold as CJC-1295 with DAC includes the albumin binding linker and clears much more slowly.