Macimorelin acetateProduct ingredient for Macimorelin

Name
Macimorelin acetate
Drug Entry
Macimorelin

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.

Accession Number
DBSALT002428
Structure
Thumb
Synonyms
Not Available
UNII
AQZ1003RMG
CAS Number
945212-59-9
Weight
Average: 534.617
Monoisotopic: 534.259068219
Chemical Formula
C28H34N6O5
InChI Key
WVDSKQXKCDZXLH-OHIDFYLOSA-N
InChI
InChI=1S/C26H30N6O3.C2H4O2/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;1-2(3)4/h3-10,13-15,22-23,28-29H,11-12,27H2,1-2H3,(H,30,33)(H,31,35)(H,32,34);1H3,(H,3,4)/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; acetic acid
SMILES
CC(O)=O.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
External Links
ChemSpider
29398956
ChEMBL
CHEMBL2364617
Wikipedia
Macimorelin
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
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon