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Purity: ≥98%
Macimorelin acetate (formerly AEZS-130; EP-1572; JMV-1843; trade name: Macrilen), the acetate salt form of Macimorelin, is a novel and potent synthetic small molecule growth hormone secretagogue receptor agonist approved in 2018 for use in the diagnosis of adult growth hormone deficiency. As a ghrelin agonist, it is orally active and stimulates the secretion of growth hormone (GH). As of December 2017, it became FDA-approved as a method to diagnose growth hormone deficiency. 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.
| ln Vivo |
In the IHKA mouse model, macimorelin perlite (5 mg/kg twice daily for 2 weeks) decreases the number and length of predictions [2].
Macimorelin Acetate is used as a diagnostic test to stimulate endogenous growth hormone (GH) secretion. In a phase III, open-label, randomized, two-way crossover trial (n=139 for efficacy analysis), a single oral dose of macimorelin (0.5 mg/kg body weight) was compared to the insulin tolerance test (ITT) for diagnosing adult growth hormone deficiency (AGHD). The macimorelin test induced a robust increase in GH levels in healthy individuals. Using a GH cutoff of 2.8 ng/mL for macimorelin and 5.1 ng/mL for ITT, the negative agreement between the tests was 95.38% (95% CI: 87.10% to 99.04%), and the positive agreement was 74.32% (95% CI: 62.84% to 83.78%). Sensitivity was 87% and specificity was 96%. In a post hoc analysis using a common cutoff of 5.1 ng/mL for both tests, the negative agreement was 93.85% (95% CI: 84.99% to 98.30%), positive agreement was 82.43% (95% CI: 71.83% to 90.30%), sensitivity was 92%, and specificity was 96%. The test showed high reproducibility (94%) in a substudy (n=33). [1] The peak GH levels after macimorelin administration were consistently higher than those after ITT across all AGHD likelihood groups (high, intermediate, low, and healthy controls). [1] |
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| Animal Protocol |
Animal/Disease Models: Intrahippocampal kainic acid (IHKA) mouse model [2]
Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection, twice a day for two weeks. Experimental Results: The number and duration of seizures were Dramatically diminished during treatment, but there was no anti-epileptogenic or disease-modifying effect. C57BL/6 male mice (10 weeks old) were used. Status epilepticus (SE) was induced by unilateral intrahippocampal stereotaxic injection of kainic acid (KA). Sham-operated mice received saline injection at the same coordinates. [2] Starting 24 hours after SE induction, mice received intraperitoneal (IP) injections of Macimorelin Acetate (5 mg/kg) or vehicle (0.9% NaCl) twice daily (between 7:00-8:00 AM and 6:00-7:00 PM) for 2 weeks. The injection volume was 10 ml/kg body weight. [2] This was followed by a 2-week wash-out period with no drug administration. Mice were continuously monitored by electroencephalogram (EEG) throughout the treatment and wash-out periods. [2] For the acute food intake experiment on day 13 of treatment, mice were observed for 2 hours immediately after morning injection, with access to pre-weighed food pellets. Time spent eating and mass of food consumed were recorded. [2] At the end of the experiment (after wash-out), mice were perfused, and brains were collected for immunohistochemical analysis of neuronal and glial markers. [2] |
| ADME/Pharmacokinetics |
Previous studies cited in this article have shown that a single oral dose of masimorelin acetate can cause a significant dose-dependent increase in growth hormone levels, lasting up to 120 minutes, with peak plasma drug concentrations occurring between 50 and 75 minutes. [1]
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| Toxicity/Toxicokinetics |
In the Phase III study, masimorelin acetate was well-tolerated and had a good safety profile. No serious adverse events (SAEs) related to masimorelin were reported. One case of arm fracture reported one day after the masimorelin trial was considered to be unrelated to the drug. The incidence and severity of non-serious adverse events (AEs) were reduced compared to the intention-to-treat (ITT) study. The most common adverse reaction was mild and transient taste disturbance (altered taste). No drug-related QT interval prolongation was recorded in this study, but a previous study reported a case of asymptomatic QT interval prolongation in a patient taking citalopram, which resolved spontaneously. [1]
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| Additional Infomation |
See also: Masimorelin (containing active ingredient).
Drug indication This drug is for diagnostic use only. GHRYVELIN is indicated for the diagnosis of adult growth hormone deficiency (GHD). Masimorelin acetate is an orally effective growth hormone-releasing peptide analog and growth hormone secretagogue (GHS). [1] It is recommended for the diagnostic test of adult growth hormone deficiency (AGHD). The test is simple to perform, requiring only oral administration and four venous blood samples to be collected at 30, 45, 60 and 90 minutes after administration for growth hormone (GH) measurement. [1] The masimorelin test is more convenient, time-saving, resource-saving and safer than the insulin tolerance test (ITT) (no risk of serious hypoglycemia). In this study, 99% of masimorelin test results were evaluable after the first attempt, whereas achieving sufficient hypoglycemia in the insulin tolerance test (ITT) was challenging. [1] The recommended GH cutoff value for the massimorelin trial using the IDS-iSYS human growth hormone (GH) assay is 5.1 ng/mL. This cutoff value strikes a good balance between sensitivity and specificity and is the same as the recommended cutoff value for the ITT using the same assay method. [1] Limitations of this study: This trial has not been evaluated in patients with poorly controlled diabetes, the elderly, children, or a large number of patients with a BMI > 35 kg/m². Further evaluation of potential interactions with QT-prolonging drugs is warranted. [1] |
| Molecular Formula |
C28H34N6O5
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| Molecular Weight |
534.62
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| Exact Mass |
534.259
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| CAS # |
945212-59-9
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| Related CAS # |
Macimorelin;381231-18-1
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| PubChem CID |
71526737
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| Appearance |
White to off-white solid powder
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| LogP |
5.156
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
39
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| Complexity |
792
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(=O)O.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
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| InChi Key |
WVDSKQXKCDZXLH-OHIDFYLOSA-N
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| InChi Code |
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
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| Chemical Name |
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8705 mL | 9.3524 mL | 18.7049 mL | |
| 5 mM | 0.3741 mL | 1.8705 mL | 3.7410 mL | |
| 10 mM | 0.1870 mL | 0.9352 mL | 1.8705 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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