:Macimorelin

{{Short description|Chemical compound}}

{{Update|date=January 2018}}

{{Infobox drug

| image = Macimorelin.svg

| pronounce =

| tradename = Macrilen

| Drugs.com = {{drugs.com|ppa|macimorelin}}

| MedlinePlus =

| DailyMedID = Macimorelin

| pregnancy_AU =

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration = By mouth

| class =

| ATC_prefix = V04

| ATC_suffix = CD06

| ATC_supplemental =

| legal_AU =

| legal_AU_comment =

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| legal_UK =

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment =

| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Macimorelin Aeterna Zentaris | website=European Medicines Agency (EMA) | date=13 November 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/macimorelin-aeterna-zentaris | access-date=28 September 2020}}{{cite web | title=Ghryvelin (previously Macimorelin Aeterna Zentaris) | website=European Medicines Agency | date=26 February 2019 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/ghryvelin-previously-macimorelin-aeterna-zentaris | access-date=15 May 2024}}

| legal_UN =

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| bioavailability =

| protein_bound =

| metabolism = Hepatic (CYP3A4-mediated)

| metabolites =

| onset =

| elimination_half-life = 4.1 hours

| duration_of_action =

| excretion =

| index2_label = as salt

| CAS_number_Ref =

| CAS_number = 381231-18-1

| CAS_supplemental = 945212-59-9 (acetate)

| PubChem = 9804938

| IUPHAR_ligand =

| DrugBank_Ref =

| DrugBank = DB13074

| ChemSpiderID_Ref =

| ChemSpiderID = 7980698

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 8680B21W73

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D10563

| KEGG2_Ref = {{keggcite|correct|kegg}}

| KEGG2 = D10562

| ChEBI_Ref =

| ChEBI =

| ChEMBL_Ref =

| ChEMBL = 278623

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = Aib-Trp-gTrp-CHO; AEZS-130; JMV 1843; Macimorelin acetate

| 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

| C=26 | H=30 | N=6 | O=3

| 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

| StdInChI = 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

| StdInChI_comment =

| StdInChIKey = UJVDJAPJQWZRFR-DHIUTWEWSA-N

| density =

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}}

Macimorelin (INN) – or Macrilen (trade name) – is a drug that was developed by Aeterna Zentaris for use in the diagnosis of adult growth hormone deficiency.{{Cite web|title=Macimorelin Aeterna Zentaris|url=https://www.ema.europa.eu/en/medicines/human/EPAR/macimorelin-aeterna-zentaris|website=www.ema.europa.eu|date=13 November 2018 }} Macimorelin acetate, the salt formulation, is a synthetic growth hormone secretagogue receptor agonist.{{Cite web|url=http://www.strongbridgebio.com/wp-content/uploads/macrilen-prescribing-information.pdf|title=Macrilen Prescribing Information|access-date=2018-07-25}} It is a growth hormone secretagogue receptor (ghrelin receptor) agonist, causing release of growth hormone from the pituitary gland.{{cite web|title=Macimorelin|url=http://www.cancer.gov/drugdictionary?cdrid=735530|work=NCI Drug Dictionary|publisher=National Cancer Institute}}{{cite journal | vauthors = Koch L | title = Growth hormone in health and disease: Novel ghrelin mimetic is safe and effective as a GH stimulation test | journal = Nature Reviews. Endocrinology | volume = 9 | issue = 6 | pages = 315 | date = June 2013 | pmid = 23591367 | doi = 10.1038/nrendo.2013.89 | s2cid = 10475359 | doi-access = free }}{{cite journal | vauthors = Garcia JM, Swerdloff R, Wang C, Kyle M, Kipnes M, Biller BM, Cook D, Yuen KC, Bonert V, Dobs A, Molitch ME, Merriam GR | display-authors = 6 | title = Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 98 | issue = 6 | pages = 2422–2429 | date = June 2013 | pmid = 23559086 | pmc = 4207947 | doi = 10.1210/jc.2013-1157 }} Macimorelin acetate is described chemically as D-Tryptophanamide, 2-methylalanyl-N-[(1R)-1-(formylamino)-2-(1H-indol-3-yl)ethyl]-acetate.

Macimorelin (Macrilen) was invented and first synthesized at University of Montpellier, Centre National de la Recherche Scientitifique (CNRS), France.{{Cite patent|title=Growth hormone secretagogues| inventor = Martinez J, Fehrentz JA, Guerlavais V |country=WO|number=2001096300|pubdate=20 December 2001 |assign=Zentaris AG | url = https://patents.google.com/patent/WO2001096300A1/en?oq=2001096300 }}{{cite journal | vauthors = Broglio F, Boutignon F, Benso A, Gottero C, Prodam F, Arvat E, Ghè C, Catapano F, Torsello A, Locatelli V, Muccioli G, Boeglin D, Guerlavais V, Fehrentz JA, Martinez J, Ghigo E, Deghenghi R | display-authors = 6 | title = EP1572: a novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in man | journal = Journal of Endocrinological Investigation | volume = 25 | issue = 8 | pages = RC26–RC28 | date = September 2002 | pmid = 12240910 | doi = 10.1007/BF03345096 | s2cid = 25962252 }}{{cite journal | vauthors = Guerlavais V, Boeglin D, Mousseaux D, Oiry C, Heitz A, Deghenghi R, Locatelli V, Torsello A, Ghé C, Catapano F, Muccioli G, Galleyrand JC, Fehrentz JA, Martinez J | display-authors = 6 | title = New active series of growth hormone secretagogues | journal = Journal of Medicinal Chemistry | volume = 46 | issue = 7 | pages = 1191–1203 | date = March 2003 | pmid = 12646029 | doi = 10.1021/jm020985q }} 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.{{Cite news | url = https://online.wsj.com/article/PR-CO-20140106-907640.html | title = Aeterna Zentaris NDA for Macimorelin Acetate in AGHD Accepted for Filing by the FDA | publisher = The Wall Street Journal | date = January 6, 2014}} The phase III trial for growth hormone deficiency is expected to be complete in December 2016.{{ClinicalTrialsGov|NCT02558829|Validation of Macimorelin as a Test for Adult Growth Hormone Deficiency}}

As of December 2017, it was FDA-approved as a method to diagnose growth hormone deficiency.{{Cite web|url=https://www.fda.gov/Drugs/InformationOnDrugs/ucm590519.htm|archive-url=https://web.archive.org/web/20180125053358/https://www.fda.gov/Drugs/InformationOnDrugs/ucm590519.htm|url-status=dead|archive-date=January 25, 2018|title=Drug Approvals and Databases - Drug Trials Snapshots: Marcrilen |website=www.fda.gov|access-date=2018-07-25}}{{Cite web|title=FDA Approves Aeterna Zentaris' Macimorelin Growth Hormone Deficiency Test|url=https://www.hcplive.com/view/fda-approves-aeterna-zentaris-macimorelin-growth-hormone-deficiency-test|access-date=2021-07-04|website=HCPLive|date=21 December 2017 }} 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 US Food and Drug Administration (FDA) considers it to be a first-in-class medication.{{cite report | title=New Drug Therapy Approvals 2017 | website=U.S. Food and Drug Administration (FDA) | date=January 2018 | url=https://www.fda.gov/media/110526/download | archive-url=https://web.archive.org/web/20190914090907/https://www.fda.gov/media/110526/download | url-status=dead | archive-date=September 14, 2019 | format=PDF | access-date=16 September 2020}}