CJC-1295

Last updated
CJC-1295
Clinical data
Routes of
administration 		Subcutaneous injection
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
Formula C152H252N44O42
Molar mass 3367.954 g·mol−1
3D model (JSmol)
  • CCC(C)C(C(=O)NC(CC1=CC=CC=C1)C(=O)NC(C(C)O)C(=O)NC(CCC(=O)N)C(=O)NC(CO)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCCN)C(=O)NC(C(C)C)C(=O)NC(CC(C)C)C(=O)NC(C)C(=O)NC(CCC(=O)N)C(=O)NC(CC(C)C)C(=O)NC(CO)C(=O)NC(C)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCCN)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(CCC(=O)N)C(=O)NC(CC(=O)O)C(=O)NC(C(C)CC)C(=O)NC(CC(C)C)C(=O)NC(CO)C(=O)NC(CCCNC(=N)N)C(=O)N)NC(=O)C(C)NC(=O)C(CC(=O)O)NC(=O)C(C)NC(=O)C(CC3=CC=C(C=C3)O)N
  • InChI=1S/C152H252N44O42/c1-22-79(15)118(194-125(214)84(20)171-135(224)107(68-115(206)207)181-124(213)81(17)169-126(215)91(155)65-87-41-45-89(201)46-42-87)147(236)189-106(66-86-34-25-24-26-35-86)141(230)196-120(85(21)200)149(238)180-99(51-54-114(158)205)132(221)190-111(72-199)145(234)185-105(67-88-43-47-90(202)48-44-88)140(229)178-96(40-33-59-168-152(164)165)128(217)177-94(37-28-30-56-154)133(222)193-117(78(13)14)146(235)187-100(60-73(3)4)134(223)170-82(18)123(212)175-97(49-52-112(156)203)130(219)183-103(63-76(9)10)138(227)191-109(70-197)143(232)172-83(19)122(211)174-95(39-32-58-167-151(162)163)127(216)176-93(36-27-29-55-153)129(218)182-102(62-75(7)8)137(226)184-101(61-74(5)6)136(225)179-98(50-53-113(157)204)131(220)186-108(69-116(208)209)142(231)195-119(80(16)23-2)148(237)188-104(64-77(11)12)139(228)192-110(71-198)144(233)173-92(121(159)210)38-31-57-166-150(160)161/h24-26,34-35,41-48,73-85,91-111,117-120,197-202H,22-23,27-33,36-40,49-72,153-155H2,1-21H3,(H2,156,203)(H2,157,204)(H2,158,205)(H2,159,210)(H,169,215)(H,170,223)(H,171,224)(H,172,232)(H,173,233)(H,174,211)(H,175,212)(H,176,216)(H,177,217)(H,178,229)(H,179,225)(H,180,238)(H,181,213)(H,182,218)(H,183,219)(H,184,226)(H,185,234)(H,186,220)(H,187,235)(H,188,237)(H,189,236)(H,190,221)(H,191,227)(H,192,228)(H,193,222)(H,194,214)(H,195,231)(H,196,230)(H,206,207)(H,208,209)(H4,160,161,166)(H4,162,163,167)(H4,164,165,168)/t79-,80-,81+,82-,83-,84-,85+,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,117-,118-,119-,120-/m0/s1
  • Key:XOZMWINMZMMOBR-HRDSVTNWSA-N

CJC-1295, also known as DAC:GRF (short for drug affinity complex:growth hormone-releasing factor), is a synthetic analogue of growth hormone-releasing hormone (GHRH) (also known as growth hormone-releasing factor (GRF)) and a growth hormone secretagogue (GHS) which was developed by ConjuChem Biotechnologies. [1] [2] [3] It is a modified form of GHRH (1-29) with improved pharmacokinetics, especially in regard to half-life. [1] [2] [3] [4]

Contents

CJC-1295 markedly increases plasma growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in both animals and humans. [1] [2] [3] [5] With a single injection, in human subjects, CJC-1295 increases plasma GH levels by 2- to 10-fold for 6 days or longer and plasma IGF-1 levels by 0.5- to 3-fold for 9 to 11 days. [3] The drug has an estimated half-life of about 6 to 8 days in humans. [3] With multiple doses of CJC-1295, IGF-1 levels were found to remain elevated in humans for up to 28 days. [3]

CJC-1295 has been shown to extend the half-life and bioavailability of growth-hormone-releasing hormone 1-29 and stimulate insulin-like growth factor 1 secretion. It increases the half-life of acting agents by bioconjugation. [6]

CJC-1295 was under investigation for the treatment of lipodystrophy and growth hormone deficiency and reached phase II clinical trials but was discontinued upon the death of one of the trial subjects. [7] [8] The attending physician of the trial believed that the most likely explanation for the incident was that the patient had asymptomatic coronary artery disease with plaque rupture and occlusion, and that the occurrence was unrelated to treatment with CJC-1295. [8] Research was terminated nonetheless as a precaution. [8] CJC-1295 has found grey market use for bodybuilding purposes, with this, in some countries such as the Netherlands, being an illicit use. [7] [9]

See also

Related Research Articles

<span class="mw-page-title-main">Growth hormone</span> Peptide hormone that stimulates growth, cell reproduction and cell regeneration

Growth hormone (GH) or somatotropin, also known as human growth hormone in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of IGF-1 and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

<span class="mw-page-title-main">Gigantism</span> Human growth disorder

Gigantism, also known as giantism, is a condition characterized by excessive growth and height significantly above average. In humans, this condition is caused by over-production of growth hormone in childhood, resulting in people up to 2.7 m (9.0 ft) in height.

<span class="mw-page-title-main">Insulin-like growth factor 1</span> Protein-coding gene in the species Homo sapiens

Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.

<span class="mw-page-title-main">Ghrelin</span> Peptide hormone involved in appetite regulation

Ghrelin is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid.

ConjuChem Biotechnologies Inc. is a medical biotechnology company located in Montreal, Quebec, Canada which is credited with inventing the experimental peptide hormone CJC-1295.

Growth hormone–releasing hormone (GHRH), also known as somatocrinin or by several other names in its endogenous forms and as somatorelin (INN) in its pharmaceutical form, is a releasing hormone of growth hormone (GH). It is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus.

<span class="mw-page-title-main">Laron syndrome</span> Medical condition

Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency (GHRD), is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 production in response to growth hormone. It is usually caused by inherited growth hormone receptor (GHR) mutations.

Sermorelin acetate, also known as GHRH (1-29), is a peptide analogue of growth hormone-releasing hormone (GHRH) which is used as a diagnostic agent to assess growth hormone (GH) secretion for the purpose of diagnosing growth hormone deficiency. It is a 29-amino acid polypeptide representing the 1–29 fragment from endogenous human GHRH, thought to be the shortest fully functional fragment of GHRH.

<span class="mw-page-title-main">Growth hormone secretagogue receptor</span> Protein-coding gene in the species Homo sapiens

Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth hormone secretagogues (GHSs), such as ghrelin, the "hunger hormone". The role of GHS-R is thought to be in regulating energy homeostasis and body weight. In the brain, they are most highly expressed in the hypothalamus, specifically the ventromedial nucleus and arcuate nucleus. GSH-Rs are also expressed in other areas of the brain, including the ventral tegmental area, hippocampus, and substantia nigra. Outside the central nervous system, too, GSH-Rs are also found in the liver, in skeletal muscle, and even in the heart.

<span class="mw-page-title-main">GHRP-6</span> Chemical compound

Growth hormone-releasing peptide 6 (GHRP-6), also known as growth hormone-releasing hexapeptide, is one of several synthetic met-enkephalin analogues that include unnatural D-amino acids, were developed for their growth hormone-releasing activity and are called growth hormone secretagogues. They lack opioid activity but are potent stimulators of growth hormone (GH) release. These secretagogues are distinct from growth hormone releasing hormone (GHRH) in that they share no sequence relation and derive their function through activation of a completely different receptor. This receptor was originally called the growth hormone secretagogue receptor (GHSR), but due to subsequent discoveries, the hormone ghrelin is now considered the receptor's natural endogenous ligand, and it has been renamed as the ghrelin receptor. Therefore, these GHSR agonists act as synthetic ghrelin mimetics.

<span class="mw-page-title-main">Growth-hormone-releasing hormone receptor</span> Receptor protein that binds with somatcrinin

The growth-hormone-releasing hormone receptor (GHRHR) is a G-protein-coupled receptor that binds growth hormone-releasing hormone. The GHRHR activates a Gs protein that causes a cascade of cAMP via adenylate cyclase. GHRHR is distinct from the growth hormone secretagogue receptor, where growth hormone releasing peptides act to release growth hormone.

<span class="mw-page-title-main">Ibutamoren</span> Experimental drug

Ibutamoren (INN) is a potent, long-acting, orally-active, selective, and non-peptide agonist of the ghrelin receptor and a growth hormone secretagogue, mimicking the growth hormone (GH)-stimulating action of the endogenous hormone ghrelin. It has been shown to increase the secretion of several hormones including GH and insulin-like growth factor 1 (IGF-1) and produces sustained increases in the plasma levels of these hormones without affecting cortisol levels.

<span class="mw-page-title-main">Tabimorelin</span> Chemical compound

Tabimorelin (INN) is a drug which acts as a potent, orally-active agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and growth hormone secretagogue, mimicking the effects of the endogenous peptide agonist ghrelin as a stimulator of growth hormone (GH) release. It was one of the first GH secretagogues developed and is largely a modified polypeptide, but it is nevertheless orally-active in vivo. Tabimorelin produced sustained increases in levels of GH and insulin-like growth factor 1 (IGF-1), along with smaller transient increases in levels of other hormones such as adrenocorticotropic hormone (ACTH), cortisol, and prolactin. However actual clinical effects in adults with growth hormone deficiency were limited, with only the most severely GH-deficient patients showing significant benefit, and tabimorelin was also found to act as a CYP3A4 inhibitor which could cause it to have undesirable interactions with other drugs.

Cyril Y. Bowers, M.D., emeritus professor of medicine at Tulane University School of Medicine, attended medical school at the University of Oregon and did an internship at the University of Washington. He then studied biochemistry at Cornell University and attended the postgraduate school of medicine at the University of Pennsylvania. From 1961-2004 he was the director of the Section of Endocrinology & Metabolism in the department of medicine at Tulane University School of Medicine. Bowers has served on the editorial board of several endocrine journals, was a member of the National Institute of Diabetes and Digestive and Kidney Diseases Study Section for eight years and has written over 400 articles in peer-reviewed journals, including chapters in books and over 200 abstracts.

Modified GRF (1-29) often abbreviated as mod GRF (1-29), originally known as tetrasubstituted GRF (1-29), is a term used to identify a 29 amino acid peptide analogue of growth-hormone-releasing hormone (GHRH), a releasing hormone of growth hormone (GH). It is a modified version of the shortest fully functional fragment of GHRH, often referred to as growth hormone releasing factor (1-29), and also known by its standardized name, sermorelin.

Growth hormone secretagogues or GH secretagogues (GHSs) are a class of drugs which act as secretagogues of growth hormone (GH). They include agonists of the ghrelin/growth hormone secretagogue receptor (GHSR), such as ghrelin (lenomorelin), pralmorelin (GHRP-2), GHRP-6, examorelin (hexarelin), ipamorelin, and ibutamoren (MK-677), and agonists of the growth hormone-releasing hormone receptor (GHRHR), such as growth hormone-releasing hormone, CJC-1295, sermorelin, and tesamorelin.

<span class="mw-page-title-main">Tesamorelin</span> Pharmaceutical drug

Tesamorelin (INN) is a synthetic form of growth-hormone-releasing hormone (GHRH) which is used in the treatment of HIV-associated lipodystrophy, approved initially in 2010. It is produced and developed by Theratechnologies, Inc. of Canada. The drug is a synthetic peptide consisting of all 44 amino acids of human GHRH with the addition of a trans-3-hexenoic acid group.

<span class="mw-page-title-main">Ipamorelin</span> Peptide selective agonist of the ghrelin/growth hormone secretagogue receptor

Ipamorelin (INN) (developmental code name NNC 26-0161) is a peptide selective agonist of the ghrelin/growth hormone secretagogue receptor (GHS) and a growth hormone secretagogue. It is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2 that was derived from GHRP-1.

<span class="mw-page-title-main">Examorelin</span> Chemical compound

Examorelin (INN) (developmental code names EP-23905, MF-6003), also known as hexarelin, is a potent, synthetic, peptidic, orally-active, centrally-penetrant, and highly selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and a growth hormone secretagogue which was developed by Mediolanum Farmaceutici. It is a hexapeptide with the amino acid sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 which was derived from GHRP-6. These GH-releasing peptides have no sequence similarity to ghrelin, but mimic ghrelin by acting as agonists at the ghrelin receptor.

<span class="mw-page-title-main">Ulimorelin</span> Chemical compound

Ulimorelin is a drug with a modified cyclic peptide structure which acts as a selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR-1a).. Unlike many related drugs, ulimorelin has little or no effect on growth hormone (GH) release in rats. However, like ghrelin and other ghrelin agonists, ulimorelin does stimulate GH release with concomitant increases in insulin-like growth factor 1 (IGF-1) in humans. It has been researched for enhancing gastrointestinal motility, especially in gastroparesis and in aiding recovery of bowel function following gastrointestinal surgery, where opioid analgesic drugs used for post-operative pain relief may worsen existing constipation. While ulimorelin has been shown to increase both upper and lower gastrointestinal motility in rats, and showed promising results initially in humans, it failed in pivotal clinical trials in post operative ileus.

References

  1. 1 2 3 Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, et al. (July 2005). "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. 146 (7): 3052–8. doi: 10.1210/en.2004-1286 . PMID   15817669.
  2. 1 2 3 Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R (December 2006). "Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse". American Journal of Physiology. Endocrinology and Metabolism. 291 (6): E1290-4. doi:10.1152/ajpendo.00201.2006. PMID   16822960.
  3. 1 2 3 4 5 6 Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA (March 2006). "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". The Journal of Clinical Endocrinology and Metabolism. 91 (3): 799–805. doi: 10.1210/jc.2005-1536 . PMID   16352683.
  4. ↑ Thorner MO (June 2008). "The discovery of growth hormone-releasing hormone: an update". Journal of Neuroendocrinology. 20 (6): 653–4. doi: 10.1111/j.1365-2826.2008.01740.x . PMID   18601685. S2CID   29788809.
  5. ↑ Ionescu M, Frohman LA (December 2006). "Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog". The Journal of Clinical Endocrinology and Metabolism. 91 (12): 4792–7. doi: 10.1210/jc.2006-1702 . PMID   17018654.
  6. ↑ "Current Research Findings Regarding CJC-1295". Neo Scientific. 2 June 2015. Archived from the original on 7 April 2019. Retrieved 3 August 2015. The reason why CJC1295 possesses the ability to lengthen the half-life within the active agent has to do with the scientific process known as bioconjugation. This technology, which is relatively new in nature, is defined by its ability to take a reactive group and bond it to a peptide (Aslam and Dent). This attachment causes a reaction with a nucleophilic unit; a typically partially molecule that is found within the bloodstream of an animal test subject. This reaction in turn causes a more stable bond to occur. This specific peptide has an especially high attraction to albumin, a globular protein that is soluble in water. This affinity prohibits natural degradation, which in turn increases the peptide's half-life (Hermanson). Additionally, clinical research performed on animal test subjects has thus far shown that there have been no signs of DPP-IV degradation present when CJC-1295 was introduced (Gonzalez, US Peptide Articles).
  7. 1 2 Hartvig RA, Holm NB, Dalsgaard PW, Reitzel LA, Müller IB, Linnet K (2014). "Identification of peptide and protein doping related drug compounds confiscated in Denmark between 2007-2013". Scandinavian Journal of Forensic Science. 20 (2): 42–49. doi: 10.2478/sjfs-2014-0003 . ISSN   2353-0707.
  8. 1 2 3 ConjuChem (August 2006). "Patient Died in Lipodystrophy Drug Study". Archived from the original on 2017-11-06. Retrieved 2015-06-13.
  9. ↑ Henninge J, Pepaj M, Hullstein I, Hemmersbach P (2010). "Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation". Drug Testing and Analysis. 2 (11–12): 647–50. doi:10.1002/dta.233. PMID   21204297.
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