Macimorelin

A summary of the most common chemical descriptors (InChI Key and SMILES codes) for Macimorelin are summarized together with 3D and 2D structures and relevant physico-chemical properties.

What is the Macimorelin?

The molecule Macimorelin presents a molecular formula of C₂₆H₃₀N₆O₃ and its IUPAC name is 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.

Macimorelin is a novel, orally active ghrelin agonist. It is the first and only FDA-approved ghrelin agonist. Macimorelin is indicated for the diagnosis of adult growth hormone deficiency (AGHD). .

Macimorelin is a peptidomimetic of ghrelin, the natural ligand of the ghrelin receptor. Ghrelin is a 28-amino acid peptide that is predominantly produced in the stomach. It is released into circulation in a pulsatile manner and is the only known circulating orexigenic hormone. The main function of ghrelin is to stimulate appetite and promote energy storage. In addition to its central role in regulating energy balance, ghrelin also regulates gastrointestinal motility, gastric acid secretion, cell proliferation and cell death, and glucose metabolism. .

The pharmacodynamic effects of macimorelin are mediated by activation of the ghrelin receptor. Ghrelin receptors are present in the hypothalamus, pituitary, and other tissues. In the pituitary, activation of the ghrelin receptor stimulates growth hormone release. .

The diagnosis of AGHD is based on the presence of low circulating levels of growth hormone. Growth hormone levels fluctuate throughout the day and are typically highest during the early morning hours. For this reason, the diagnosis of AGHD is typically made using the insulin tolerance test (ITT) or the growth hormone stimulation test (GHST). .

The ITT is the gold standard for the diagnosis of AGHD. However, the ITT is an invasive test that requires the administration of insulin and frequent blood draws. The GHST is a newer, non-invasive test that uses macimorelin to stimulate growth hormone release. .

Macimorelin is administered orally in a dose of 0.3 mg/kg. A fasting blood sample is drawn 30 minutes after administration. Growth hormone levels are then measured and compared to the normal range. .

The use of macimorelin for the diagnosis of AGHD is safe and well tolerated. The most common side effects are headache, dizziness, nausea, and fatigue. .

Macimorelin is a novel, orally active ghrelin agonist that is indicated for the diagnosis of AGHD. It is the first and only FDA-approved ghrelin agonist. Macimorelin is safe and well tolerated. The most common side effects are headache, dizziness, nausea, and fatigue..

3D structure

Cartesian coordinates

Geometry of Macimorelin in x, y and z coordinates (Å units) to copy/paste elsewhere. Generated with Open Babel software.

2D drawing

Molecule descriptors

Other names (synonyms)

IUPAC nomenclature provides a standardized method for naming chemical compounds. Although this system is widely used in chemistry, many chemical compounds have also other names commonly used in different contexts. These synonyms can come from a variety of sources and are used for a variety of purposes.

One common source of synonyms for chemical compounds is the common or trivial names, assigned on the basis of appearance, properties, or origin of the molecule.

Another source of synonyms are historical or obsolete names employed in the past, however replaced nowadays by more modern or standardized names.

In addition to common and historical names, chemical compounds may also have synonyms that are specific to a particular field or industry.

Reference codes for other databases

• CAS number (Chemical Abstracts Service Registry Number) is a unique identifier is assigned to every chemical compound indexed in the CAS database.
• Beilstein: The Beilstein database is a comprehensive source of information on organic chemistry, including information on chemical structures, properties, and reactions. The Beilstein database assigns unique identifiers which can be used to identify compounds in scientific literature and other sources.
• ChEBI (Chemical Entities of Biological Interest): ChEBI is a database of small chemical molecules that are of interest in the field of biology.
• PubChem CID (Compound Identifier): PubChem is a database of chemical compounds that is maintained by the National Institutes of Health (NIH).
• RTECS number (Registry of Toxic Effects of Chemical Substances): The RTECS is a database of information on the toxic effects of chemicals, including information on their structures and properties.
• ChEMBL (Compound Bioactivity Data): ChEMBL is a database of bioactivity data for small molecules, including information on their properties and structures.
• CompTox Dashboard (Environmental Protection Agency): The CompTox Dashboard is a database of information on the toxicology and environmental effects of chemicals.

Physico-Chemical properties

LogP and topological polar surface area (TPSA) values were estimated using Open Babel software.

The n-octanol/water partition coeficient (K_ow) data is applied in toxicology and drug research. K_ow values are used, to guess the environmental fate of persistent organic pollutants. High partition coefficients values, tend to accumulate in the fatty tissue of organisms. Molecules with a log(K_ow) (or LogP) greater than 5 are considered to bioaccumulate.

TPSA values are the sum of the surface area over all polar atoms or molecules, mainly oxygen and nitrogen, also including hydrogen atoms.

In medicinal chemistry, TPSA is used to assess the ability of a drug to permeabilise cells.

For molecules to penetrate the blood-brain barrier (and act on receptors in the central nervous system), TPSA values below 90 Ų are required. Thus, molecules with a polar surface area greater than 140 Ų tend to be poorly permeable to cell membranes.