| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 32±3 nM (GHS-R1a, in LLC-PK1 cells)[1]
Targets the ghrelin receptor, GHS-R1a, as a selective antagonist. It exhibits potent activity in LLC-PK1 cells, with an IC50 of 32 +/- 3 nM. It is a competitive antagonist, as it does not induce any intracellular calcium mobilization by itself, confirming that it lacks agonistic activity and acts purely as a blocker of ghrelin‘s effects. |
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| ln Vitro |
With an IC50 of 32 nM, JMV 2959 is an antagonist of growth hormone secretagogue receptor type 1a (GHS-R1a). By itself, JMV 2959 is unable to cause any intracellular calcium mobilization. The Schild method is used to determine the receptor/JMV 2959 complex's dissociation constant. The dissociation constant Kb, as determined by this experiment, is 19±6 nM[1].
In vitro, JMV 2959 hydrochloride effectively blocks the effects of ghrelin at the GHS-R1a. By competing with ghrelin for binding to the receptor, it prevents the downstream signaling pathways that lead to increased intracellular calcium. The dissociation constant (Kb) of the receptor/JMV 2959 complex, determined by the Schild method, is 19 +/- 6 nM, confirming its high affinity and competitive mechanism of action. |
| ln Vivo |
Ghrelin (0.033, 0.1, and 0.33 mg/kg) administered intraperitoneally (ip) has no effect on rats' prepulse inhibition (PPI) or auditory startle reactions (ASR). On the other hand, dose-dependently increasing PPI and decreasing ASR is seen with intraperitoneal injection of JMV 2959 (1, 3, and 6 mg/kg). While pretreatment with the highest dose of Ghrelin does not potentiate or change PPI responses of a sub-threshold dose of PCP (0.75 mg/kg), pretreatment with JMV 2959 at a level that has no effect on ASR or PPI per se entirely inhibits Phencyclidine (PCP)-induced (2 mg/kg) deficits in PPI[2].
In vivo, JMV 2959 is used to block ghrelin‘s effects. While ip administration of ghrelin (0.033, 0.1, and 0.33 mg/kg) does not alter acoustic startle responses in rats, injection of JMV 2959 can be used to assess whether any observed physiological effects are indeed mediated by GHS-R1a. This makes it a key tool for establishing the ghrelin-dependence of a response. |
| Enzyme Assay |
While cell-free radioligand binding assays can be performed, this is a classical GPCR antagonist. Typically, membranes from GHS-R1a-transfected cells are incubated with a radiolabeled ghrelin agonist and increasing concentrations of cold JMV 2959. The concentration required to displace 50% of the specific binding (IC50) is determined, from which the Ki is calculated.
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| Cell Assay |
To confirm pure antagonism, LLC-PK1 cells expressing the GHS-R1a are loaded with a calcium-sensitive fluorescent dye. The cells are then treated with JMV 2959 alone, and any change in fluorescence (indicative of calcium mobilization) is measured. A lack of response confirms the antagonist lacks any inherent agonist activity.
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| Animal Protocol |
No specific animal studies for this compound are publicly detailed. A common protocol for a GHS-R1a antagonist would be to establish a ghrelin-induced effect in a rodent model (e.g., on feeding behavior) and then pre-treat the animals with JMV 2959. If the antagonist blocks the ghrelin-induced effect, it confirms the specificity of the response. Endpoints would include food intake, body weight, or other behavioral parameters.
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| ADME/Pharmacokinetics |
Detailed PK data for JMV 2959 hydrochloride is not publicly available. As a small molecule (MW 545.08), it is likely to have some degree of oral bioavailability. The hydrochloride salt form is intended to improve its solubility and stability for in vivo administration, but no formal PK parameters have been published.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for JMV 2959 hydrochloride. As a research-grade antagonist, no safety studies have been published. It is likely to be well-tolerated in acute experiments, but its pharmacological action of blocking ghrelin could theoretically lead to decreased appetite, weight loss, and alterations in metabolism and reward pathways.
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| References |
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| Additional Infomation |
JMV 2959 hydrochloride is a research-grade chemical and is not approved for clinical use. It is a valuable tool for investigating the role of the ghrelin system in regulating food intake, energy balance, drug reward and addiction, and gastrointestinal motility. It is one of the most widely used GHS-R1a antagonists in the field.
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| Molecular Formula |
C30H33CLN6O2
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|---|---|
| Molecular Weight |
545.075025320053
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| Exact Mass |
544.235
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| CAS # |
2448414-54-6
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| Related CAS # |
JMV 2959;925238-89-7
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| PubChem CID |
72193865
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
39
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| Complexity |
726
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| Defined Atom Stereocenter Count |
1
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| SMILES |
COC1=CC=C(C=C1)CN2C(=NN=C2[C@@H](CC3=CNC4=CC=CC=C43)NC(=O)CN)CCC5=CC=CC=C5.Cl
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| InChi Key |
QRRDZYKIVMLOJQ-HZPIKELBSA-N
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| InChi Code |
InChI=1S/C30H32N6O2.ClH/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);1H/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;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: 250 mg/mL (458.65 mM)
H2O: 25 mg/mL (45.86 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.82 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.82 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (183.46 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8346 mL | 9.1730 mL | 18.3459 mL | |
| 5 mM | 0.3669 mL | 1.8346 mL | 3.6692 mL | |
| 10 mM | 0.1835 mL | 0.9173 mL | 1.8346 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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