| Size | Price | Stock | Qty |
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| Targets |
MCHr1 antagonist 2 targets the melanin-concentrating hormone receptor 1 (MCH1-R) with an IC50 of 65 nM. It also inhibits the hERG potassium channel with an IC50 of 4.0 nM in IMR-32 cells. The compound shows inhibitory effects on calcium flux with an IC50 of 196 ± 30 nM in the same cell line. By antagonizing MCHr1, it blocks the downstream signaling of melanin-concentrating hormone, which is involved in regulating feeding behavior and energy balance.
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| ln Vitro |
Compound 30, also known as MCHR1 Antagonist 2, has an IC50 of 65 nM, making it an antagonist of melanin-concentrating hormone receptor 1. With an IC50 of 196 ± 30 nM and 4.0 ± 0.8 nM, respectively, MCHR1 antagonist 2 inhibits both Ca2+ flow and hERG in IMR-32 cells [1].
In vitro, MCHr1 antagonist 2 (Compound 30) is an antagonist of melanin concentrating hormone receptor 1, with an IC50 of 65 nM. It has inhibitory effects on Ca2+ flux, and hERG, with IC50s of 196 ± 30 nM and 4.0 ± 0.8 nM, respectively, in IMR-32 cells. The compound demonstrates potent antagonistic activity against MCHr1, making it a useful tool for studying the physiological and pathological roles of the MCH system in cell-based assays. |
| ln Vivo |
In vivo activity data for MCHr1 antagonist 2 is not detailed in the publicly available sources. As a potent MCHr1 antagonist with demonstrated in vitro activity, it is hypothesized to exhibit effects on feeding behavior, energy expenditure, and potentially sleep regulation in animal models. However, specific in vivo efficacy studies, including pharmacokinetic and pharmacodynamic parameters, have not been reported. Further research is needed to fully characterize its in vivo activity and therapeutic potential.
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| Enzyme Assay |
For cell-free assays, the binding affinity of MCHr1 antagonist 2 to the MCH1 receptor can be measured using radioligand binding assays. Membrane preparations from cells expressing the receptor are incubated with a radiolabeled ligand and varying concentrations of the compound. The IC50 value is calculated from a competition binding curve. Its inhibitory effect on hERG can be assessed using electrophysiology techniques such as patch-clamp on cells expressing the hERG channel, or using fluorescence-based membrane potential assays.
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| Cell Assay |
For in vitro cellular assays, the antagonistic activity of MCHr1 antagonist 2 can be assessed in cells expressing the MCH1 receptor, such as IMR-32 cells. Cells are loaded with a calcium-sensitive fluorescent dye and treated with varying concentrations of the compound. The inhibition of MCH-induced calcium flux is measured using a fluorometric imaging plate reader. The IC50 for receptor antagonism is calculated from concentration-response curves. The selectivity of the compound can be assessed by testing against a panel of related receptors.
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| Animal Protocol |
For in vivo studies, MCHr1 antagonist 2 could be administered orally or intraperitoneally in animal models of obesity, diabetes, or sleep disorders. In obesity models, endpoints include food intake, body weight, and metabolic parameters. In sleep models, endpoints include sleep-wake cycles and EEG recordings. Its effect on cardiovascular safety can be assessed by measuring QT interval prolongation in telemetered animals, given its hERG inhibitory activity.
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| ADME/Pharmacokinetics |
MCHr1 antagonist 2 (CAS 863115-70-2) has a molecular formula of C23H21FN2O5 and a molecular weight of 424.42 g/mol. Its chemical name is N-{1-[(2H-1,3-benzodioxol-5-yl)methyl]piperidin-4-yl}-6-fluoro-4-oxo-4H-chromene-2-carboxamide. Purity is typically ≥98%. Solubility: DMSO: 10 mg/mL (23.56 mM; ultrasonic and adjust pH to 6 with HCl). Storage: Dry, dark and -20°C for 1 year. In vivo formulation: 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% Saline: 1 mg/mL.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available. As a potent hERG inhibitor with an IC50 of 4.0 nM, there is a significant potential for cardiotoxicity, specifically QT interval prolongation. This is a major concern for drug development and would necessitate thorough cardiovascular safety assessments. Standard toxicological profiling, including hERG and in vivo cardiovascular studies, would be required for further development.
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| References | |
| Additional Infomation |
MCHr1 antagonist 2 is a research-grade compound and is not approved for therapeutic use. It serves primarily as a pharmacological tool for studying the MCH system, feeding behavior, and energy homeostasis. Its mechanism of action involves antagonism of the MCH1 receptor. No clinical trials have been reported. The compound is of interest for the potential treatment of obesity, diabetes, and sleep disorders. Due to its potent hERG inhibition, its development as a therapeutic agent would face significant challenges.
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| Molecular Formula |
C23H21FN2O5
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|---|---|
| Molecular Weight |
424.421649694443
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| Exact Mass |
424.143
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| CAS # |
863115-70-2
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| PubChem CID |
11464405
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| Appearance |
White to off-white solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
31
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| Complexity |
723
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C2C(=CC=C(C=2)F)OC(C(NC2CCN(CC3C=C4C(OCO4)=CC=3)CC2)=O)=C1
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| InChi Key |
HHCYCBKPWYJVEB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H21FN2O5/c24-15-2-4-19-17(10-15)18(27)11-22(31-19)23(28)25-16-5-7-26(8-6-16)12-14-1-3-20-21(9-14)30-13-29-20/h1-4,9-11,16H,5-8,12-13H2,(H,25,28)
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| Chemical Name |
N-[1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-yl]-6-fluoro-4-oxochromene-2-carboxamide
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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 : ~10 mg/mL (~23.56 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.36 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.36 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 10.0 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. View More
Solubility in Formulation 3: ≥ 1 mg/mL (2.36 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 | 2.3562 mL | 11.7808 mL | 23.5616 mL | |
| 5 mM | 0.4712 mL | 2.3562 mL | 4.7123 mL | |
| 10 mM | 0.2356 mL | 1.1781 mL | 2.3562 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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