Identification
- Summary
Macimorelin is a medication used to treat adult growth hormone deficiency.
- Brand Names
- Macrilen
- Generic Name
- Macimorelin
- DrugBank Accession Number
- DB13074
- Background
Macimorelin, a novel and orally active ghrelin mimetic that stimulates GH secretion, is used in the diagnosis of adult GH deficiency (AGHD). More specifically, macimorelin is a peptidomimetic growth hormone secretagogue (GHS) that acts as an agonist of GH secretagogue receptor, or ghrelin receptor (GHS-R1a) to dose-dependently increase GH levels 3. Growth hormone secretagogues (GHS) represent a new class of pharmacological agents which have the potential to be used in numerous clinical applications. They include treatment for growth retardation in children and cachexia associated with chronic disease such as AIDS and cancer.
Growth hormone (GH) is classically linked with linear growth during childhood. In deficiency of this hormone, AGHD is commonly associated with increased fat mass (particularly in the abdominal region), decreased lean body mass, osteopenia, dyslipidemia, insulin resistance, and/or glucose intolerance overtime. In addition, individuals with may be susceptible to cardiovascular complications from altered structures and function 5. Risk factors of AGHD include a history of childhood-onset GH deficiency or with hypothalamic/pituitary disease, surgery, or irradiation to these areas, head trauma, or evidence of other pituitary hormone deficiencies 3. While there are various therapies available such as GH replacement therapy, the absence of panhypopituitarism and low serum IGF-I levels with nonspecific clinical symptoms pose challenges to the detection and diagnosis of AGHD. The diagnosis of AGHD requires biochemical confirmation with at least 1 GH stimulation test 3. Macimorelin is clinically useful since it displays good stability and oral bioavailability with comparable affinity to ghrelin receptor as its endogenous ligand. In clinical studies involving healthy subjects, macimorelin stimulated GH release in a dose-dependent manner with good tolerability 3.
Macimorelin, developed by Aeterna Zentaris, was approved by the FDA in December 2017 under the market name Macrilen for oral solution.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Macimorelin (DB13074)
- Weight
- Average: 474.565
Monoisotopic: 474.23793885 - Chemical Formula
- C26H30N6O3
- Synonyms
- Macimorelin
- External IDs
- ARD 07
- ARD-07
- D-87575
- EP 1572
- EP-01572
- EP-1572
- JMV-1843
Pharmacology
- Indication
Indicated for the diagnosis of adult growth hormone deficiency (AGHD) Label.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Adult growth hormone deficiency •••••••••••• - Contraindications & Blackbox Warnings
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Maximum GH levels from stimulation are observed between 30 to 90 minutes after administration of macimorelin Label. Increase in the QTcF interval may be observed from macimorelin administration Label.
- Mechanism of action
Ghrelin is an endogenous ligand for the GH secretagogue receptor that is also called the ghrelin receptor (GHS-R1a). Upon activation of the receptor, ghrelin serves to increase growth hormone (GH) secretion. Macimorelin mimics the actions of ghrelin by stimulating GH release. As a synthetic agonist, it activates growth hormone secretagogue receptors present in the pituitary and hypothalamus.
Target Actions Organism UGrowth hormone secretagogue receptor type 1 agonistHumans - Absorption
Macimorelin is a novel, synthetic ghrelin agonist, which is readily absorbed from the gastrointestinal tract 4. The maximum plasma concentration (Cmax) was observed between 0.5 and 1.5 hours following oral administration of 0.5mg/kg macimorelin to patients with AGHD under fasting for at least 8 hours. Higher doses of drug demonstrate a dose-proportional increase in plasma concentrations 4. A liquid meal decreased the macimorelin Cmax and AUC by 55% and 49%, respectively Label.
- Volume of distribution
Following a single oral dose of 0.5 mg/kg macimorelin, the mean volume of distribution of the central compartment is 5,733.4 ± 565.7L 4.
- Protein binding
Not Available
- Metabolism
Macimorelin predominantly undergoes CYP3A4-mediated metabolism according to an in vitro human liver microsomes study Label.
- Route of elimination
Not Available
- Half-life
The mean terminal half-life (T1/2) is 4.1 hours following administration of a single oral dose of 0.5 mg macimorelin/kg body weight in healthy subjects Label.
- Clearance
Following a single oral dose of 0.5 mg/kg macimorelin, the mean clearance over the fraction absorbed (Cl/F) was 37,411.0 ± 4,554.6 mL/min 4.
- Adverse Effects
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Macimorelin has not shown to demonstrate mutagenic properties according to bacterial assays. It also did not induce any mutations or clastogenic effects in mouse lymphoma cells with or without metabolic activation. Studies assessing the carcinogenic potential or effect on fertility of macimorelin have not been conducted Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Macimorelin can be increased when it is combined with Abametapir. Aceclofenac The therapeutic efficacy of Macimorelin can be decreased when used in combination with Aceclofenac. Acemetacin The therapeutic efficacy of Macimorelin can be decreased when used in combination with Acemetacin. Acetylsalicylic acid The therapeutic efficacy of Macimorelin can be decreased when used in combination with Acetylsalicylic acid. Aclidinium The therapeutic efficacy of Macimorelin can be decreased when used in combination with Aclidinium. - Food Interactions
- Avoid St. John's Wort. This herb induces the CYP3A metabolism of macimorelin and may reduce its serum concentration, which may cause a false-positive test result.
- Take on an empty stomach. Fast for at least eight hours before taking macimorelin.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Macimorelin acetate AQZ1003RMG 945212-59-9 WVDSKQXKCDZXLH-OHIDFYLOSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Macimorelin Aeterna Zentaris Granule 60 mg Oral Consilient Health Limited 2021-01-12 Not applicable EU 
Macrilen Granule, for solution 60 mg/1mg Oral Novo Nordisk 2022-01-31 2027-02-28 US 
Macrilen Granule, for solution 60 mg/1mg Oral Strongbridge U.S. Inc 2018-01-29 Not applicable US
Categories
- ATC Codes
- V04CD06 — Macimorelin
- Drug Categories
- Amino Acids
- Amino Acids, Aromatic
- Amino Acids, Cyclic
- Amino Acids, Peptides, and Proteins
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Diagnostic Agents
- Growth Hormone Secretagogue Receptor Agonist
- Growth Hormone Secretagogue Receptor Agonists
- Heterocyclic Compounds, Fused-Ring
- Highest Risk QTc-Prolonging Agents
- QTc Prolonging Agents
- Tests for Pituitary Function
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Dipeptides
- Alternative Parents
- N-acyl-alpha amino acids and derivatives / Tryptamines and derivatives / Alpha amino acid amides / 3-alkylindoles / Substituted pyrroles / Fatty amides / Benzenoids / Heteroaromatic compounds / Secondary carboxylic acid amides / Azacyclic compounds show 4 more
- Substituents
- 3-alkylindole / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-dipeptide / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 8680B21W73
- CAS number
- 381231-18-1
- InChI Key
- UJVDJAPJQWZRFR-DHIUTWEWSA-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
- IUPAC Name
- (2R)-2-(2-amino-2-methylpropanamido)-3-(1H-indol-3-yl)-N-[(1R)-2-(1H-indol-3-yl)-1-formamidoethyl]propanamide
- SMILES
- CC(C)(N)C(=O)N[C@H](CC1=CNC2=CC=CC=C12)C(=O)N[C@H](CC1=CNC2=CC=CC=C12)NC=O
References
- General References
- Guerlavais V, Boeglin D, Mousseaux D, Oiry C, Heitz A, Deghenghi R, Locatelli V, Torsello A, Ghe C, Catapano F, Muccioli G, Galleyrand JC, Fehrentz JA, Martinez J: New active series of growth hormone secretagogues. J Med Chem. 2003 Mar 27;46(7):1191-203. [Article]
- Broglio F, Boutignon F, Benso A, Gottero C, Prodam F, Arvat E, Ghe C, Catapano F, Torsello A, Locatelli V, Muccioli G, Boeglin D, Guerlavais V, Fehrentz JA, Martinez J, Ghigo E, Deghenghi R: EP1572: a novel peptido-mimetic GH secretagogue with potent and selective GH-releasing activity in man. J Endocrinol Invest. 2002 Sep;25(8):RC26-8. [Article]
- Garcia JM, Swerdloff R, Wang C, Kyle M, Kipnes M, Biller BM, Cook D, Yuen KC, Bonert V, Dobs A, Molitch ME, Merriam GR: Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2013 Jun;98(6):2422-9. doi: 10.1210/jc.2013-1157. Epub 2013 Apr 4. [Article]
- Piccoli F, Degen L, MacLean C, Peter S, Baselgia L, Larsen F, Beglinger C, Drewe J: Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects. J Clin Endocrinol Metab. 2007 May;92(5):1814-20. doi: 10.1210/jc.2006-2160. Epub 2007 Feb 6. [Article]
- Fukuda I, Hizuka N, Muraoka T, Ichihara A: Adult growth hormone deficiency: current concepts. Neurol Med Chir (Tokyo). 2014;54(8):599-605. Epub 2014 Jul 28. [Article]
- External Links
- KEGG Drug
- D10563
- ChemSpider
- 7980698
- BindingDB
- 50125886
- 1999420
- ChEMBL
- CHEMBL278623
- ZINC
- ZINC000001554197
- Wikipedia
- Macimorelin
- FDA label
- Download (280 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Diagnostic Diagnosis of Adult Growth Hormone Deficiency (AGDH) 1 3 Completed Diagnostic Growth Hormone Deficiency With Pituitary Anomalies 1 3 Recruiting Diagnostic Human Growth Hormone Deficiency 1 2 Completed Treatment Cancer Cachexia 1 1 Completed Treatment Healthy Subjects (HS) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Granule, for suspension Oral 60 MG Granule Oral 60 mg Granule, for solution Oral 60 mg/1mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8192719 No 2012-06-05 2027-10-12 US US6861409 No 2005-03-01 2022-08-01 US
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00616 mg/mL ALOGPS logP 1.77 ALOGPS logP 1.67 Chemaxon logS -4.9 ALOGPS pKa (Strongest Acidic) 12.4 Chemaxon pKa (Strongest Basic) 8.34 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 144.9 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 133.14 m3·mol-1 Chemaxon Polarizability 49.05 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0000900000-f5f1e7009cd5e8727a7a Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00dv-0264900000-5b79212ceedac00fd78a Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0111900000-e62b67445a25fc5272a2 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0f6x-8649400000-43643d9ec1ce7dcd18ee Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-1911000000-0b38cdbdbaacd807deda Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00l6-4962100000-28fb78c29927f29d24dd Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 200.50554 predictedDeepCCS 1.0 (2019) [M+H]+ 202.90111 predictedDeepCCS 1.0 (2019) [M+Na]+ 208.81364 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Peptide hormone binding
- Specific Function
- Receptor for ghrelin, coupled to G-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-...
- Gene Name
- GHSR
- Uniprot ID
- Q92847
- Uniprot Name
- Growth hormone secretagogue receptor type 1
- Molecular Weight
- 41328.045 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
Drug created at October 21, 2016 02:42 / Updated at February 21, 2021 18:54