Macimorelin

Identification

Summary

Macimorelin is a medication used to treat adult growth hormone deficiency.

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
Thumb
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.

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
Pharmacodynamics

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.

TargetActionsOrganism
UGrowth hormone secretagogue receptor type 1
agonist
Humans
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
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity

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
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbametapirThe serum concentration of Macimorelin can be increased when it is combined with Abametapir.
AceclofenacThe therapeutic efficacy of Macimorelin can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Macimorelin can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Macimorelin can be decreased when used in combination with Acetylsalicylic acid.
AclidiniumThe therapeutic efficacy of Macimorelin can be decreased when used in combination with Aclidinium.
AcrivastineThe risk or severity of QTc prolongation can be increased when Acrivastine is combined with Macimorelin.
AdenosineThe risk or severity of QTc prolongation can be increased when Adenosine is combined with Macimorelin.
AjmalineThe risk or severity of QTc prolongation can be increased when Ajmaline is combined with Macimorelin.
AlclofenacThe therapeutic efficacy of Macimorelin can be decreased when used in combination with Alclofenac.
AlfuzosinThe risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Macimorelin.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
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

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Product Ingredients
IngredientUNIICASInChI Key
Macimorelin acetateAQZ1003RMG945212-59-9WVDSKQXKCDZXLH-OHIDFYLOSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Macimorelin Aeterna ZentarisGranule60 mgOralAeterna Zentaris Gmb H2021-01-12Not applicableEU flag
MacrilenGranule, for solution60 mg/1mgOralStrongbridge U.S. Inc2018-01-29Not applicableUS flag
MacrilenGranule, for solution60 mg/1mgOralNovo Nordisk2020-11-30Not applicableUS flag

Categories

ATC Codes
V04CD06 — Macimorelin
Drug Categories
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
KEGG Drug
D10563
ChemSpider
7980698
BindingDB
50125886
RxNav
1999420
ChEMBL
CHEMBL278623
ZINC
ZINC000001554197
Wikipedia
Macimorelin
FDA label
Download (280 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedDiagnosticDiagnosis of Adult Growth Hormone Deficiency (AGDH)1
3CompletedDiagnosticGrowth Hormone Deficiency With Pituitary Anomalies1
3Not Yet RecruitingDiagnosticHuman Growth Hormone Deficiency1
3Not Yet RecruitingTreatmentAdult Onset Growth Hormone Deficiency / Mild Traumatic Brain Injury (MTBI)1
2Active Not RecruitingTreatmentCancer Cachexia1
1CompletedTreatmentHealthy Volunteers1
Not AvailableCompletedDiagnosticPolyuria-polydipsia Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
GranuleOral60 mg
Granule, for suspensionOral
Granule, for solutionOral60 mg/1mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8192719No2012-06-052027-10-12US flag
US6861409No2005-03-012022-08-01US flag

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00616 mg/mLALOGPS
logP1.77ALOGPS
logP1.67ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)12.4ChemAxon
pKa (Strongest Basic)8.34ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area144.9 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity133.14 m3·mol-1ChemAxon
Polarizability49.05 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Learn more
Accelerate your drug discovery research with our ADMET & drug target dataset
Learn more
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 on October 21, 2016 02:42 / Updated on February 21, 2021 18:54