| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
D3 Receptor ( EC50 = 38 nM )
D3 dopamine receptor (D3R) - highly selective agonist (EC50 = 38 nM). |
|---|---|
| ln Vitro |
ML417 displays a Ki of 1.24 µM for the D3R. For numerous signaling pathways connected to D3R activation, ML417 is a complete and powerful agonist[1].
ML417 potently inhibits the accumulation of cAMP with an EC50 of 86 nM and an efficacy equivalent to dopamine. ML417 shows submicromolar affinity for just three targets: σ-1, 5-HT2B serotoninergic, and β1-adrenergic receptors. ML417 promotes β-arrestin recruitment to the D3R-WT with an EC50 of 1.4 nM[1]. ML417 (0.005–5 μM; 24 hours) D3R-expressing dopaminergic neurons are shielded from 6-OHDA-induced cell death[1]. In vitro studies demonstrate that ML417 is a highly selective, brain-penetrant agonist of the D3 dopamine receptor (D3R) with an EC50 of 38 nM. The compound potently promotes D3R-mediated β-arrestin translocation, G protein-mediated signaling, and ERK1/2 phosphorylation (pERK) with minimal effects on other GPCR-mediated signaling. ML417 exhibits very limited cross-reactivity at other GPCRs, including the dopamine D2 receptor (EC50 > 10,000 nM), indicating exceptional selectivity for D3R. The compound's ability to activate both G protein-dependent and β-arrestin-dependent signaling pathways makes it a valuable tool for studying D3R signaling mechanisms and their role in dopaminergic neurotransmission. |
| ln Vivo |
In vivo pharmacokinetics experiments in mice (using 20 mg/kg; i.p.) reveals that ML417 is brain penetrant and exhibits a plasma half-life of 3.44 hours and a brain half-life of 4.23 hours. In vivo pharmacokinetics experiments in mice (using 20 mg/kg; i.p.) reveals that ML417 is brain penetrant and exhibits a plasma half-life of 3.44 hours and a brain half-life of 4.23 hours. ML417 exhibits a brain Tmax of 0.25 hours and a Cmax of 28000 ng/ml, in addition to a plasma Tmax of 0.5 hours and a Cmax of 6500 ng/ml[1].
In vivo studies have demonstrated that ML417 exhibits neuroprotective activity against toxin-induced neurodegeneration of dopaminergic neurons. This effect is mediated through D3R activation, which has been shown to promote neuronal survival and protect against dopaminergic cell death in models of Parkinson's disease. The compound's brain penetrance and selectivity for D3R over other dopamine receptors make it a valuable tool for studying the role of D3R in neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, and addiction. The compound's neuroprotective properties suggest potential therapeutic applications for conditions involving dopaminergic neuron degeneration. |
| Enzyme Assay |
For receptor binding studies, competitive binding assays are performed using membrane preparations from cells expressing the D3 dopamine receptor or using radiolabeled ligands such as [3H]-spiperone. Membranes are incubated with the radioligand and varying concentrations of ML417. Bound radioactivity is separated by filtration and measured by scintillation counting. Binding affinity (Ki) is calculated from competition curves. For functional studies, cells expressing D3R are treated with ML417, and β-arrestin translocation (using BRET or PathHunter technology), G protein activation (using GTPγS binding assays), and ERK1/2 phosphorylation (by Western blotting) are measured. EC50 values are calculated from dose-response curves.
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| Cell Assay |
Cellular assays for ML417 typically involve culturing cells that express the D3 dopamine receptor (recombinant or endogenous). Cells are treated with ML417 at various concentrations, and receptor activation is assessed by measuring β-arrestin translocation (using BRET or PathHunter assays), cAMP accumulation (using ELISA or HTRF-based cAMP assays), or ERK1/2 phosphorylation (by Western blotting). Neuroprotective effects are evaluated in dopaminergic neuronal cell lines (such as SH-SY5Y) treated with neurotoxins (e.g., MPP+ or 6-OHDA) in the presence or absence of ML417. Cell viability is assessed using MTT or CellTiter-Glo assays. Selectivity over other dopamine receptors and GPCRs is confirmed using similar assay formats.
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| Animal Protocol |
6-8 week old male C57BL/6 mice
20 mg/kg I.p. (Pharmacokinetic Analysis) In vivo efficacy of ML417 is evaluated in animal models of Parkinson's disease and other neurological disorders. For neuroprotection studies, mice or rats are treated with neurotoxins such as MPTP or 6-OHDA to induce dopaminergic neuron degeneration, and then treated with ML417 via intraperitoneal or oral administration. Dopaminergic neuron survival is assessed by immunohistochemistry for tyrosine hydroxylase (TH) in the substantia nigra and striatum. Behavioral tests such as the rotarod test, open field test, and apomorphine-induced rotation test are used to assess motor function. For other indications, appropriate disease models are used to evaluate the compound's efficacy. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of ML417 have been characterized to support its use as a research tool. The compound is brain-penetrant, which is essential for studying central nervous system targets. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and brain tissue samples following administration. The compound's molecular weight of 379.45 and chemical properties influence its absorption, distribution, metabolism, and excretion (ADME) characteristics. The compound's ability to reach therapeutic concentrations in the brain is important for its neuroprotective effects.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of ML417 is typically conducted in parallel with efficacy studies in animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of mammalian cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs, and histopathological examination of major organs. As a D3 dopamine receptor agonist, potential effects on motor function, behavior, and the cardiovascular system are carefully monitored. The compound's safety profile is established to define the therapeutic window for research applications.
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| References | |
| Additional Infomation |
ML417 is a research tool compound used for studying D3 dopamine receptor function and its role in neurological and psychiatric disorders. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves selective and potent agonism of the D3 dopamine receptor, which activates both G protein-dependent and β-arrestin-dependent signaling pathways, leading to neuroprotective effects and modulation of dopaminergic neurotransmission. This compound is valuable for investigating the therapeutic potential of D3R modulation in Parkinson's disease, schizophrenia, addiction, and other conditions involving the dopaminergic system.
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| Molecular Formula |
C22H25N3O3
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|---|---|
| Molecular Weight |
379.45220541954
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| Exact Mass |
379.19
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| Elemental Analysis |
C, 69.64 H, 6.64 N, 11.07 O, 12.65
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| CAS # |
1386162-69-1
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| PubChem CID |
27842480
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| Appearance |
Solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
501
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC=C(C=C1)OCCN2CCN(CC2)C(=O)C3=CC4=CC=CC=C4N3
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| InChi Key |
HAZPAMUWUHDPDA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H25N3O3/c1-27-18-6-8-19(9-7-18)28-15-14-24-10-12-25(13-11-24)22(26)21-16-17-4-2-3-5-20(17)23-21/h2-9,16,23H,10-15H2,1H3
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| Chemical Name |
1H-indol-2-yl-[4-[2-(4-methoxyphenoxy)ethyl]piperazin-1-yl]methanone
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| Synonyms |
ML417; ML-417; ML 417
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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: ~50 mg/mL (~131.8 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (13.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6354 mL | 13.1770 mL | 26.3539 mL | |
| 5 mM | 0.5271 mL | 2.6354 mL | 5.2708 mL | |
| 10 mM | 0.2635 mL | 1.3177 mL | 2.6354 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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