CJC-1295

CJC-1295
Peptide sequence of CJC-1295 showed with 3-letter nomenclature and fully specified DAC (side-chain extended lysine)
Clinical data
Other namesCJC-1295 with DAC
Routes of
administration		Subcutaneous injection
ATC code
  • None
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC165H269N47O46
Molar mass3647.250 g·mol−1
3D model (JSmol)
  • NC([C@H](CCCCNC(CCN1C(C=CC1=O)=O)=O)NC([C@H](CCCNC(N)=N)NC([C@H](CO)NC([C@H](CC(C)C)NC([C@@]([C@H](CC)C)([H])NC([C@@H](NC([C@H](CCC(N)=O)NC([C@H](CC(C)C)NC([C@H](CC(C)C)NC([C@H](CCCCN)NC([C@H](CCCNC(N)=N)NC([C@@H](NC([C@H](CO)NC([C@H](CC(C)C)NC([C@H](CCC(N)=O)NC([C@@H](NC([C@H](CC(C)C)NC([C@H](C(C)C)NC([C@H](CCCCN)NC([C@H](CCCNC(N)=N)NC([C@@H](NC([C@H](CO)NC([C@H](CCC(N)=O)NC([C@@]([C@@H](C)O)([H])NC([C@@H](NC([C@@]([C@H](CC)C)([H])NC([C@@H](NC([C@@H](NC([C@H](NC([C@@H](N[H])CC2=CC=C(O)C=C2)=O)C)=O)CC(O)=O)=O)C)=O)=O)CC3=CC=CC=C3)=O)=O)=O)=O)CC4=CC=C(O)C=C4)=O)=O)=O)=O)=O)C)=O)=O)=O)=O)C)=O)=O)=O)=O)=O)=O)CC(O)=O)=O)=O)=O)=O)=O)=O
  • InChI=1S/C165H269N47O46/c1-22-87(15)130(209-137(233)92(20)185-148(244)116(76-127(225)226)196-136(232)89(17)183-138(234)99(168)73-95-44-48-97(217)49-45-95)160(256)204-115(74-94-36-25-24-26-37-94)154(250)211-132(93(21)216)162(258)195-108(54-57-123(171)221)145(241)205-120(80-215)158(254)200-114(75-96-46-50-98(218)51-47-96)153(249)192-105(43-35-66-182-165(177)178)141(237)191-102(40-28-31-62-167)146(242)208-129(86(13)14)159(255)202-109(68-81(3)4)147(243)184-90(18)135(231)189-106(52-55-121(169)219)143(239)198-112(71-84(9)10)151(247)206-118(78-213)156(252)186-91(19)134(230)188-103(41-33-64-180-163(173)174)140(236)190-101(39-27-30-61-166)142(238)197-111(70-83(7)8)150(246)199-110(69-82(5)6)149(245)194-107(53-56-122(170)220)144(240)201-117(77-128(227)228)155(251)210-131(88(16)23-2)161(257)203-113(72-85(11)12)152(248)207-119(79-214)157(253)193-104(42-34-65-181-164(175)176)139(235)187-100(133(172)229)38-29-32-63-179-124(222)60-67-212-125(223)58-59-126(212)224/h24-26,36-37,44-51,58-59,81-93,99-120,129-132,213-218H,22-23,27-35,38-43,52-57,60-80,166-168H2,1-21H3,(H2,169,219)(H2,170,220)(H2,171,221)(H2,172,229)(H,179,222)(H,183,234)(H,184,243)(H,185,244)(H,186,252)(H,187,235)(H,188,230)(H,189,231)(H,190,236)(H,191,237)(H,192,249)(H,193,253)(H,194,245)(H,195,258)(H,196,232)(H,197,238)(H,198,239)(H,199,246)(H,200,254)(H,201,240)(H,202,255)(H,203,257)(H,204,256)(H,205,241)(H,206,247)(H,207,248)(H,208,242)(H,209,233)(H,210,251)(H,211,250)(H,225,226)(H,227,228)(H4,173,174,180)(H4,175,176,181)(H4,177,178,182)/t87-,88-,89+,90-,91-,92-,93+,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,129-,130-,131-,132-/m0/s1
  • Key:ZUQGTWKGESAQCD-ZGFIGYLBSA-N

CJC-1295 DAC, 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]

Effects

CJC-1295 may markedly increase plasma growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in animals and humans.[1][2][3][5] With a single injection, in human subjects, CJC-1295 DAC may increase 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] With the inclusion of the DAC additive, 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] The extended half-life is achieved through the addition of a drug affinity complex (DAC) that binds to albumin, thus prolonging the peptide's presence in the bloodstream.[7][8][9] It is primarily used for its potential to stimulate the release of growth hormone (GH) from the pituitary gland.[10]

Risks

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.[11][12] 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.[12] Research was terminated nonetheless as a precaution.[12] CJC-1295 has found grey market use for bodybuilding purposes, with this, in some countries such as the Netherlands, being an illicit use.[11][13]

Structure

CJC-1295 and Modified GRF (1-29) is equated falsely in several scientific papers.[14][15] CJC-1295, CJC-1295 DAC, and CJC-1295 with DAC are synonyms, while Modified GRF (1-29), also known as CJC-1295 without DAC, lacks the C-terminus extension with Nɛ-maleimidopropionyl-Lysine, which is referred to as DAC.[16]

The IUPAC modification nomenclature for the peptide CJC-1295 is Nɛ30-maleimidopropionyl-[D-Ala2, Gln8, Ala15, Leu27]-Sermorelin-Lys30.

Sermorelin: H-Tyr-Ala2-Asp-Ala-Ile-Phe-Thr-Asn8-Ser-Tyr-Arg-Lys-Val-Leu-Gly15-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met27-Ser-Arg-NH2

CJC-1295 without DAC: H-Tyr-D-Ala2-Asp-Ala-Ile-Phe-Thr-Gln8-Ser-Tyr-Arg-Lys-Val-Leu-Ala15-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu27-Ser-Arg-NH2

CJC-1295: H-Tyr-D-Ala2-Asp-Ala-Ile-Phe-Thr-Gln8-Ser-Tyr-Arg-Lys-Val-Leu-Ala15-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu27-Ser-Arg-(Nɛ-maleimidopropionyl-)Lys30-NH2

See also

References

  1. ^ a b c 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. ^ a b c Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, et al. (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. ^ a b c d e f 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. ^ Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V (November 2021). "Advances in the detection of growth hormone releasing hormone synthetic analogs". Drug Testing and Analysis. 13 (11–12): 1871–1887. doi:10.1002/dta.3183. PMID 34665524.
  8. ^ Hu ZY, Wang WJ, Hu L, Shi JH, Jiang SL (April 2024). "Comprehending the intermolecular interaction of dacomitinib with bovine serum albumin: experimental and theoretical approaches". Journal of Biomolecular Structure & Dynamics. 42 (7): 3579–3592. doi:10.1080/07391102.2023.2218926. PMID 37288787.
  9. ^ 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): 3052–3058. doi:10.1210/en.2004-1286. PMID 15817669.
  10. ^ Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ (December 2009). "Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects". Growth Hormone & IGF Research. 19 (6): 471–477. doi:10.1016/j.ghir.2009.03.001. PMC 2787983. PMID 19386527.
  11. ^ a b 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.
  12. ^ a b c ConjuChem (August 2006). "Patient Died in Lipodystrophy Drug Study". Archived from the original on 2017-11-06. Retrieved 2015-06-13.
  13. ^ 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.
  14. ^ Thomas A, Walpurgis K, Tretzel L, Brinkkötter P, Fichant E, Delahaut P, et al. (2015). "Expanded test method for peptides >2 kDa employing immunoaffinity purification and LC-HRMS/MS". Drug Test Anal. 7 (11–12): 990–8. doi:10.1002/dta.1868. PMID 26382721.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V (2021). "Advances in the detection of growth hormone releasing hormone synthetic analogs". Drug Test Anal. 13 (11–12): 1871–1887. doi:10.1002/dta.3183. PMID 34665524.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA (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". J Clin Endocrinol Metab. 91 (3): 799–805. doi:10.1210/jc.2005-1536. PMID 16352683.{{cite journal}}: CS1 maint: multiple names: authors list (link)