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RESEARCH ARTICLE
Contents Vol 73(4)

From JMV-1843 to Macrilen

Jean Martinez A B and Jean-Alain Fehrentz A
+ Author Affiliations
- Author Affiliations

A Institut des Biomolécules Max Mousseron (IBMM), UMR CNRS 5247, Université Montpellier, ENSCM, Montpellier 34720, France.

B Corresponding author. Email: jean.martinez@umontpellier.fr

Australian Journal of Chemistry 73(4) 334-337 https://doi.org/10.1071/CH19530
Submitted: 17 October 2019  Accepted: 25 November 2019   Published: 21 January 2020

Abstract

Growth hormone deficiency (GHD) is a severe pathology that greatly affects the quality of life, and increases morbidity and mortality of patients owing to the augmentation of cardiovascular events. Treatment of GHD is challenging, mainly because there is no specific characteristic sign or symptom that can be used to make a clear diagnosis. There is need for an unequivocal diagnosis of GHD to avoid unnecessary treatment with GH, because the available provocative tests (GH stimulation tests) are not specific and sensitive enough, and are contraindicated in some patients. Ghrelin is an endogenous peptide that stimulates GH secretion by interacting with a G-protein-coupled receptor named ghrelin receptor (GH secretagogue receptor 1a, GHS-R1a). Given this, a GH stimulation test using ghrelin or its analogues appears to be attractive. In this paper, a modified tripeptide first named JMV-1843 in the laboratory is briefly presented. It is potent and selective in stimulating the release of GH and is orally active. It has been recently commercialised for the diagnosis of adult GH deficiency under the tradename Macrilen. The test using this compound appears to be reliable, well tolerated, and simple.


References

[1]  A. S. Bates, W. Van’t Hoff, P. J. Jones, R. N. Clayton, J. Clin. Endocrinol. Metab. 1996, 81, 169.

[2]  P. V. Carroll, E. R. Christ, B. A. Bengtsson, L. Carlsson, J. S. Christiansen, D. Clemmons, R. Hintz, K. Ho, Z. Laron, P. Sizonenko, P. H. Sönksen, T. Tanaka, M. Thorner, J. Clin. Endocrinol. Metab. 1998, 83, 382.
         | Crossref | GoogleScholarGoogle Scholar | 9467546PubMed |

[3]  Communication Ætherna Zentaris Inc., Quebec City, 7 August 2012 .

[4]  K. Stochholm, C. H. Gravholt, T. Laursen, J. O. Jørgensen, P. Laurberg, M. Andersen, L. Ø. Kristensen, U. Feldt-Rasmussen, J. S. Christiansen, M. Frydenberg, A. Green, Eur. J. Endocrinol. 2006, 155, 61.
         | Crossref | GoogleScholarGoogle Scholar | 16793951PubMed |

[5]  K. C. J. Yuen, N. A. Tritos, S. L. Samson, A. R. Hoffman, L. Katznelson, Endocr. Pract. 2016, 22, 1235.
         | Crossref | GoogleScholarGoogle Scholar |

[6]  S. Melmed, J. Clin. Endocrinol. Metab. 2013, 98, 2187.
         | Crossref | GoogleScholarGoogle Scholar | 23539718PubMed |

[7]  K. K. Ho, Eur. J. Endocrinol. 2007, 157, 695.
         | Crossref | GoogleScholarGoogle Scholar | 18057375PubMed |

[8]  V. Agrawal, J. M. Garcia, Expert Rev. Mol. Diagn. 2014, 14, 647.
         | Crossref | GoogleScholarGoogle Scholar | 24834478PubMed |

[9]  B. M. K. Biller, M. H. Samuels, A. Zagar, D. M. Cook, B. M. Arafah, V. Bonert, S. Stavrou, D. L. Kleinberg, J. J. Chipman, M. L. Hartman, J. Clin. Endocrinol. Metab. 2002, 87, 2067.
         | Crossref | GoogleScholarGoogle Scholar |

[10]  M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, K. Kangawa, Nature 1999, 402, 656.
         | Crossref | GoogleScholarGoogle Scholar | 10604470PubMed |

[11]  A. D. Howard, S. D. Feighner, D. F. Cully, J. P. Arena, P. A. Liberator, C. Y. Rosemblum, M. Hamelin, D. L. Hreniuk, O. C. Palyha, J. Anderson, P. S. Paress, et al. Science 1996, 273, 974.
         | Crossref | GoogleScholarGoogle Scholar | 8688086PubMed |

[12]  A. J. van der Lely, M. Tschop, M. L. Heiman, E. Ghigo, Endocr. Rev. 2004, 25, 426.
         | Crossref | GoogleScholarGoogle Scholar | 15180951PubMed |

[13]  G. Muccioli, M. Tschöp, M. Papotti, R. Deghenghi, M. Heiman, E. Ghigo, Eur. J. Pharmacol. 2002, 440, 235.
         | Crossref | GoogleScholarGoogle Scholar | 12007539PubMed |

[14]  E. Arvat, M. Maccario, L. Di Vito, F. Broglio, A. Benso, C. Gottero, M. Papotti, G. Muccioli, C. Dieguez, F. F. Casanueva, R. Deghenghi, F. Camanni, E. Ghigo, J. Clin. Endocrinol. Metab. 2001, 86, 1169.
         | 11238504PubMed |

[15]  R. Deghenghi, Acta Paediatr. 1997, 86, 85.
         | Crossref | GoogleScholarGoogle Scholar |

[16]  M. Rodriguez, P. Dubreuil, J.-P. Bali, J. Martinez, J. Med. Chem. 1987, 30, 758.
         | Crossref | GoogleScholarGoogle Scholar | 3572963PubMed |

[17]  V. Guerlavais, D. Boeglin, D. Mousseaux, C. Oiry, A. Heitz, R. Deghenghi, V. Locatelli, A. Torsello, C. Ghe, F. Catapano, G. Muccioli, J.-C. Galleyrand, J.-A. Fehrentz, J. Martinez, J. Med. Chem. 2003, 46, 1191.
         | Crossref | GoogleScholarGoogle Scholar | 12646029PubMed |

[18]  F. Broglio, F. Boutignon, A. Benso, C. Gottero, F. Prodam, E. Arvat, C. Ghe, F. Catapano, A. Torsello, V. Locatelli, G. Muccioli, D. Boeglin, V. Guerlavais, J.-A. Fehrentz, J. Martinez, E. Ghigo, R. Deghenghi, J. Endocrinol. Invest. 2002, 25, RC26.
         | Crossref | GoogleScholarGoogle Scholar | 12240910PubMed |

[19]  E. Arvat, J. Ramunni, R. Giordano, B. Maccagno, F. Broglio, A. Benso, R. Deghenghi, E. Ghigo, J. Endocrinol. Invest. 1999, 22, 23.
         | Crossref | GoogleScholarGoogle Scholar | 10090133PubMed |

[20]  B. Holst, E. Brandt, A. Bach, A. Heding, T. W. Schawrtz, Mol. Endocrinol. 2005, 19, 2400.
         | Crossref | GoogleScholarGoogle Scholar | 15905359PubMed |

[21]  F. Piccoli, L. Degen, C. MacLean, S. Peter, L. Baselgia, F. Larsen, C. Beglinger, J. Drewe, J. Clin. Endocrinol. Metab. 2007, 92, 1814.
         | Crossref | GoogleScholarGoogle Scholar | 17284637PubMed |

[22]  S. Mary, J.-A. Fehrentz, M. Damian, G. Gaibelet, H. Orcel, P. Verdié, B. Mouillac, J. Martinez, J. Marie, J.-L. Banères, J. Biol. Chem. 2013, 288, 24656.
         | Crossref | GoogleScholarGoogle Scholar | 23839942PubMed |

[23]  M. Damian, V. Pons, P. Renault, C. M’Kadmi, B. Delort, L. Hartmann, A. I. Kaya, M. Louet, D. Gagne, K. B. H. Salah, S. Denoyelle, G. Ferry, J. A. Boutin, R. Wagner, J.-A. Fehrentz, J. Martinez, J. Marie, N. Floquet, C. Galès, S. Mary, H. E. Hamm, J.-L. Banères, Proc. Natl. Acad. Sci. USA 2018, 115, 4501.
         | Crossref | GoogleScholarGoogle Scholar | 29632174PubMed |

[24]  European Medicines Agency, Science Medicines Health, EMA/CHMP/845216/2018, Committee for Medicinal Products for Human Use (CHMP), 15 November 2018 .

[25]  G. R. Gabreanu, Discoveries (Craiova) 2018, 6, e82.
         | Crossref | GoogleScholarGoogle Scholar |

[26]  US Food and Drug Administration, NDA approval, NDA 205598, 20 December 2017 . Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205598s000lbl.pdf (accessed 31 March 2018)