| Size | Price | Stock | Qty |
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| Targets |
JMV-2959 targets the growth hormone secretagogue receptor type 1a (GHS-R1a), also known as the ghrelin receptor. GHS-R1a is a G protein-coupled receptor that is activated by ghrelin, a peptide hormone produced primarily in the stomach. Ghrelin stimulates the release of growth hormone from the pituitary gland and promotes appetite and food intake. By antagonizing GHS-R1a, JMV-2959 blocks the binding of ghrelin and inhibits its downstream signaling. The compound has an IC50 of 32 nM for GHS-R1a, indicating high potency. JMV-2959 is a selective antagonist, as it does not induce intracellular calcium mobilization, a hallmark of GHS-R1a activation. This pure antagonistic activity is important for studying the effects of blocking ghrelin signaling without confounding agonist effects. The compound's ability to modulate GHS-R1a activity makes it a valuable tool for studying the role of ghrelin in various physiological processes, including metabolism, appetite regulation, and neuropsychiatric disorders.
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| ln Vitro |
JMV 2959 is an IC50 of 32 nM growth fish rescue hormone 1a (GHS-R1a) restricted antagonist. JMV 2959 does not cause a calcium charge to occur inside cells [1].
JMV-2959 demonstrates potent in vitro activity as a GHS-R1a antagonist. It has an IC50 of 32 nM for GHS-R1a, indicating high potency. Importantly, JMV-2959 does not induce any intracellular calcium mobilization by itself, confirming that it is a pure antagonist and not an agonist. This distinguishes it from compounds that have partial agonist activity. The compound's antagonistic activity has been confirmed in cell-based assays using cells expressing GHS-R1a. In these assays, JMV-2959 inhibits the effects of ghrelin, such as calcium mobilization and signaling pathway activation. These in vitro findings establish JMV-2959 as a potent and selective GHS-R1a antagonist. |
| ln Vivo |
Furthermore, it does not significantly boost the release of growth hormone (GH) or enhance food intake [1]. JMV 2959 enhanced the percentage of prepulse inhibition (PPI) and dose-dependently decreased the startle reaction in the prepulse inhibition paradigm. The main cause of the modified startle response was the 27% decrease in startle that was seen at the maximum dosage of JMV 2959 (6 mg/kg) in comparison to the baseline drug [2]. Significant locomotor inhibition was generated by 6 mg/kg JMV 2959 on days 1 through 7, as compared to baseline day 0. Additionally, a significant interaction between JMV 2959 therapy and day was found in the results [3].
JMV-2959 demonstrates significant in vivo activity, consistent with its antagonism of GHS-R1a. It does not significantly promote growth hormone (GH) release or increase food intake, which are the hallmark effects of ghrelin agonism. This confirms that JMV-2959 is a functional antagonist in vivo. The compound has been shown to reduce the startle response and enhance prepulse inhibition (PPI) in a dose-dependent manner. PPI is a measure of sensorimotor gating, and its disruption is a hallmark of schizophrenia. The enhancement of PPI by JMV-2959 suggests that it may have antipsychotic potential. Additionally, JMV-2959 produces significant locomotor inhibition in animal models. These in vivo effects highlight the compound's potential for the treatment of neuropsychiatric disorders. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assay for JMV-2959 typically involves assessing its affinity for GHS-R1a using radioligand binding techniques. In a typical protocol, membrane preparations from cells expressing GHS-R1a are incubated with a radiolabeled ligand (e.g., [125I]-ghrelin) and varying concentrations of JMV-2959. After incubation, the bound and free radioligand are separated by filtration or centrifugation, and the radioactivity is measured. The displacement of the radioligand by JMV-2959 is used to calculate its binding affinity (IC50). For JMV-2959, this method has been used to determine its IC50 of 32 nM for GHS-R1a. These binding studies are critical for characterizing the compound's affinity and selectivity for its target.
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| Cell Assay |
The in vitro cellular assay for JMV-2959 typically involves evaluating its effects on GHS-R1a-mediated signaling. In a typical assay, cells expressing GHS-R1a are loaded with a calcium-sensitive fluorescent dye and then treated with ghrelin in the presence of varying concentrations of JMV-2959. The intracellular calcium concentration is measured as an indicator of receptor activation. JMV-2959 inhibits the ghrelin-induced calcium signal in a concentration-dependent manner. Importantly, JMV-2959 does not induce calcium mobilization by itself, confirming its pure antagonistic activity. These cellular assays are crucial for confirming the compound's functional activity as an antagonist.
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| Animal Protocol |
The in vivo animal experimental protocol for JMV-2959 typically involves the use of rodent models to assess its effects on behavior and physiology. In a typical study, JMV-2959 is administered to mice or rats, and its effects on startle response and prepulse inhibition (PPI) are measured. The compound reduces the startle response and enhances PPI in a dose-dependent manner. Its effects on locomotor activity are also assessed, and JMV-2959 produces significant locomotor inhibition. For studying its effects on food intake and growth hormone release, animals are treated with JMV-2959, and food consumption and serum GH levels are measured. The results show that JMV-2959 does not significantly affect these parameters, consistent with its antagonistic activity. These in vivo models are essential for demonstrating the compound's pharmacological effects in a whole-organism context.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic (PK) data for JMV-2959, such as half-life, clearance, volume of distribution, or bioavailability, are not reported in the available literature. However, the compound's in vivo effects after systemic administration suggest that it reaches sufficient concentrations to exert its pharmacological effects. JMV-2959 has a molecular weight of 508.61 and is soluble in DMSO. Further studies are needed to fully characterize the PK properties of JMV-2959.
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| Toxicity/Toxicokinetics |
Specific toxicity (toxicology) data for JMV-2959 are not reported in the available literature. However, the compound's in vivo effects have been studied at doses up to 6 mg/kg without reported significant adverse effects. Comprehensive toxicological assessments would be necessary to fully evaluate the safety profile of JMV-2959 for potential therapeutic applications. The compound is for research use only.
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| References |
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| Additional Infomation |
JMV-2959 is a growth hormone secretagogue receptor type 1a (GHS-R1a) antagonist with an IC50 of 32 nM. It does not induce intracellular calcium mobilization, indicating pure antagonistic activity. In vivo, it does not promote GH release or increase food intake, but it reduces startle response, enhances prepulse inhibition, and produces locomotor inhibition. The compound has a molecular formula of C30H32N6O2 and a molecular weight of 508.61. JMV-2959 is used as a pharmacological tool to study the role of GHS-R1a in metabolism, behavior, and neurological disorders.
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| Molecular Formula |
C30H32N6O2
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| Molecular Weight |
508.614086151123
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| Exact Mass |
508.258
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| CAS # |
925238-89-7
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| Related CAS # |
JMV 2959 hydrochloride;2448414-54-6
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| PubChem CID |
16114404
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
38
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| Complexity |
726
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(N[C@@H](C1N(CC2=CC=C(OC)C=C2)C(CCC2=CC=CC=C2)=NN=1)CC1C2=C(NC=1)C=CC=C2)(=O)CN
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| InChi Key |
OZSZELOMMMKWTM-HHHXNRCGSA-N
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| InChi Code |
InChI=1S/C30H32N6O2/c1-38-24-14-11-22(12-15-24)20-36-28(16-13-21-7-3-2-4-8-21)34-35-30(36)27(33-29(37)18-31)17-23-19-32-26-10-6-5-9-25(23)26/h2-12,14-15,19,27,32H,13,16-18,20,31H2,1H3,(H,33,37)/t27-/m1/s1
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| Chemical Name |
2-amino-N-[(1R)-2-(1H-indol-3-yl)-1-[4-[(4-methoxyphenyl)methyl]-5-(2-phenylethyl)-1,2,4-triazol-3-yl]ethyl]acetamide
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| Synonyms |
JMV-2959; JMV 2959; JMV2959
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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 |
| 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) |
DMSO : ~25 mg/mL (~49.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9661 mL | 9.8307 mL | 19.6614 mL | |
| 5 mM | 0.3932 mL | 1.9661 mL | 3.9323 mL | |
| 10 mM | 0.1966 mL | 0.9831 mL | 1.9661 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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