Macimorelin

Macimorelin (INN) – or Macrilen (trade name) – is a drug that was developed by Æterna Zentaris for use in the diagnosis of adult growth hormone deficiency.[2] Macimorelin acetate, the salt formulation, is a synthetic growth hormone secretagogue receptor agonist.[3] It is a growth hormone secretagogue receptor (ghrelin receptor) agonist causing release of growth hormone from the pituitary gland.[4][5][6] Macimorelin acetate is described chemically as D-Tryptophanamide, 2-methylalanyl-N-[(1R)-1-(formylamino)-2-(1H-indol-3-yl)ethyl]-acetate.

Macimorelin
Clinical data
Trade namesMacrilen
Other namesAib-Trp-gTrp-CHO; AEZS-130; JMV 1843; Macimorelin acetate
AHFS/Drugs.comProfessional Drug Facts
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismHepatic (CYP3A4-mediated)
Elimination half-life4.1 hours
Identifiers
IUPAC name
  • 2-Amino-N-[(2R)-1-[[(1R)-1-formamido-2-(1H-indol-3-yl)ethyl]amino]-3-1H-indol-3-yl)-1-oxopropan-2-yl]-2-methylpropanamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC26H30N6O3
Molar mass474.565 g·mol−1
3D model (JSmol)
SMILES
  • CC(C)(C(=O)N[C@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@H](CC3=CNC4=CC=CC=C43)NC=O)N
InChI
  • InChI=1S/C26H30N6O3/c1-26(2,27)25(35)31-22(11-16-13-28-20-9-5-3-7-18(16)20)24(34)32-23(30-15-33)12-17-14-29-21-10-6-4-8-19(17)21/h3-10,13-15,22-23,28-29H,11-12,27H2,1-2H3,(H,30,33)(H,31,35)(H,32,34)/t22-,23-/m1/s1
  • Key:UJVDJAPJQWZRFR-DHIUTWEWSA-N

Macimorelin (Macrilen™) was invented and first synthesized by the research group of Professor Martinez at University of Montpellier, Centre National de la Recherche Scientitifique (CNRS), France.[7][8][9] This transpired from a long-lasting research collaboration with Aeterna Zentaris. Aeterna Zentaris later in-licensed macimorelin as a development candidate from the CNRS and proceeded with the pre-clinical and clinical development of the compound.

As of January 2014, it was in Phase III clinical trials.[10] The phase III trial for growth hormone deficiency is expected to be complete in December 2016.[11]

As of December 2017, it became FDA-approved as a method to diagnose growth hormone deficiency.[12][13] Traditionally, growth hormone deficiency was diagnosed via means of insulin tolerance test (IST) or glucagon stimulation test (GST). These two means are done parenterally, whereas Macrilen boasts an oral formulation for ease of administration for patients and providers.

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[14]

See also

References
  1. "Macimorelin Aeterna Zentaris". European Medicines Agency (EMA). 13 November 2018. Retrieved 28 September 2020.
  2. "Macimorelin Aeterna Zentaris". www.ema.europa.eu.{{cite web}}: CS1 maint: url-status (link)
  3. "Macrilen Prescribing Information" (PDF). Retrieved 2018-07-25.
  4. "Macimorelin". NCI Drug Dictionary. National Cancer Institute.
  5. Koch L (June 2013). "Growth hormone in health and disease: Novel ghrelin mimetic is safe and effective as a GH stimulation test". Nature Reviews. Endocrinology. 9 (6): 315. doi:10.1038/nrendo.2013.89. PMID 23591367. S2CID 10475359.
  6. Garcia JM, Swerdloff R, Wang C, Kyle M, Kipnes M, Biller BM, et al. (June 2013). "Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency". The Journal of Clinical Endocrinology and Metabolism. 98 (6): 2422–9. doi:10.1210/jc.2013-1157. PMC 4207947. PMID 23559086.
  7. WO 2001096300, Martinez, Jean; Fehrentz, Jean-Alain & Guerlavais, Vincent, "Growth hormone secretagogues", published 2001-12-20, assigned to Zentaris AG
  8. Broglio, F.; Boutignon, F.; Benso, A.; Gottero, C.; Prodam, F.; Arvat, E.; Ghè, C.; Catapano, F.; Torsello, A.; Locatelli, V.; Muccioli, G. (September 2002). "EP1572: A novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in man". Journal of Endocrinological Investigation. 25 (8): RC26–RC28. doi:10.1007/BF03345096. ISSN 0391-4097. PMID 12240910. S2CID 25962252.
  9. Guerlavais, Vincent; Boeglin, Damien; Mousseaux, Delphine; Oiry, Catherine; Heitz, Annie; Deghenghi, Romano; Locatelli, Vittorio; Torsello, Antonio; Ghé, Corrado; Catapano, Filomena; Muccioli, Giampiero (March 2003). "New Active Series of Growth Hormone Secretagogues". Journal of Medicinal Chemistry. 46 (7): 1191–1203. doi:10.1021/jm020985q. ISSN 0022-2623. PMID 12646029.
  10. "Aeterna Zentaris NDA for Macimorelin Acetate in AGHD Accepted for Filing by the FDA". Wall Street Journal. January 6, 2014.
  11. Clinical trial number NCT02558829 for "Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency" at ClinicalTrials.gov
  12. Center for Drug Evaluation and Research. "Drug Approvals and Databases - Drug Trials Snapshots: Marcrilen". www.fda.gov. Retrieved 2018-07-25.
  13. "FDA Approves Aeterna Zentaris' Macimorelin Growth Hormone Deficiency Test". HCPLive. Retrieved 2021-07-04.
  14. New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 2020.


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