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| Targets |
NMI 8739 targets the dopamine D2 autoreceptor, a G protein-coupled receptor that regulates dopamine synthesis and release in the brain. As a D2 autoreceptor agonist, the compound activates presynaptic D2 receptors, which inhibits dopamine synthesis and release through negative feedback mechanisms. This targeting of D2 autoreceptors makes NMI 8739 potentially useful for modulating dopamine signaling in conditions such as Parkinson's disease, schizophrenia, and other neuropsychiatric disorders. The compound's unique structure as an amine conjugate of DHA and dopamine may also provide additional effects related to the DHA carrier. NMI 8739's activity has been characterized in various in vitro systems.
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| ln Vitro |
NMI 8739 is a dopamine D2 autoreceptor agonist[1], which is an amine conjugation of the DHA carrier and the neurotransmitter dopamine[2]. NMI 8739 decreases nitric oxide (NO) generation in LPS-stimulated RAW264.7 macrophages. NMI 8739 produced concentration-dependent suppression of CCL-20, MCP-1, and IL-6 production in RAW264.7 macrophages following LPS stimulation. PGE2 production was suppressed in a concentration-dependent manner, with a 25.3% drop at 100 nM NMI 8739 and a 75% reduction at 1 μM NMI 8739. 2 μM NMI 8739 significantly suppressed IL-6 and CCL-20 release by up to 49% and 37%, respectively [3].
NMI 8739 demonstrates potent in vitro activity as a dopamine D2 autoreceptor agonist. The compound reduces nitric oxide production in LPS-stimulated RAW264.7 macrophages. It causes concentration-dependent inhibition of CCL-20, MCP-1, and IL-6 release. These effects suggest that NMI 8739 has anti-inflammatory properties in addition to its dopamine receptor activity. The compound's activity is concentration-dependent, with effects observed at appropriate concentrations. NMI 8739 is characterized as an amine conjugate of the DHA carrier and the neurotransmitter dopamine. Its unique structure may contribute to its biological activity profile. The compound's in vitro activity has been described in research publications. |
| ln Vivo |
In vivo activity of NMI 8739 has been studied in the context of its potential applications in neuropsychiatric disorders. As a dopamine D2 autoreceptor agonist, the compound would be expected to modulate dopamine signaling in the brain. The DHA carrier component of the molecule may provide additional benefits related to omega-3 fatty acid biology. NMI 8739 has been studied for its potential in conditions such as Parkinson's disease and schizophrenia. The compound's ability to modulate dopamine signaling and reduce inflammatory markers suggests potential therapeutic applications. Comprehensive in vivo efficacy data have been reported in research publications. The compound's unique structure as a DHA-dopamine conjugate may provide a novel approach to treating neuropsychiatric disorders.
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| Enzyme Assay |
In vitro receptor binding assays for NMI 8739 involve measuring binding affinity to dopamine D2 receptors. Membranes from cells expressing the D2 receptor are incubated with a radiolabeled D2 ligand and varying concentrations of the test compound. Bound and free radioligand are separated by filtration, and radioactivity is measured. Binding affinity (Ki) is calculated from competition curves using non-linear regression analysis. Functional assays can measure receptor activation by assessing inhibition of cAMP accumulation or other second messenger responses. Selectivity assays compare the compound's activity against other dopamine receptor subtypes and related receptors. Each concentration is typically tested in duplicate or triplicate. The compound's activity as a D2 autoreceptor agonist has been characterized.
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| Cell Assay |
In vitro cellular assays for NMI 8739 are performed using various cell lines to assess its biological activity. For dopamine receptor assays, cells expressing D2 receptors are treated with varying concentrations of the compound, and receptor activation is measured by inhibition of forskolin-stimulated cAMP accumulation. For anti-inflammatory assays, RAW264.7 macrophages are stimulated with LPS and treated with NMI 8739. Nitric oxide production is measured using the Griess reagent. Cytokine levels (CCL-20, MCP-1, IL-6) are measured by ELISA. Cytotoxicity is assessed in parallel using standard viability assays to ensure that observed effects are not due to cell death. EC50 values are calculated from dose-response curves.
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| Animal Protocol |
In vivo animal studies for NMI 8739 are conducted using rodent models of neuropsychiatric disorders. The compound is administered via intraperitoneal injection, subcutaneous injection, or oral gavage at various doses and schedules. Behavioral tests are used to assess the compound's effects on dopamine-mediated behaviors, including tests of motor function, cognition, and anxiety. Dopamine levels in the brain can be measured by microdialysis or tissue analysis. Inflammatory markers can be measured in serum or tissue samples. Pharmacokinetic studies assess drug concentrations in plasma and brain tissue. Animals are monitored for clinical signs and body weight. Efficacy is expressed as improvement in behavioral or biochemical parameters compared to vehicle-treated controls.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NMI 8739 have been characterized in preclinical studies. The compound has a molecular formula of C30H41NO3 and a molecular weight consistent with its structure. Its chemical name is (4Z,7Z,10Z,13Z,16Z,19Z)-N-[2-(3,4-dihydroxyphenyl)ethyl]docosa-4,7,10,13,16,19-hexaenamide. NMI 8739 is soluble in DMSO and other organic solvents. The compound is typically administered by injection due to its polarity. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and bioavailability have been characterized in animal models. The compound's ability to cross the blood-brain barrier is relevant for its central nervous system effects. Its pharmacokinetic profile supports its use as a research tool.
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| Toxicity/Toxicokinetics |
NMI 8739 is intended for laboratory research use only and has not undergone comprehensive toxicology testing. As a dopamine receptor agonist, the compound would be expected to have effects on dopamine signaling and associated behaviors. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. The compound's effects on dopamine signaling could have implications for motor function and behavior. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies has not been reported in the public domain. The compound is not approved for human use and is strictly intended for research purposes.
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| References |
[1]. Gill Higgins, New drugs signal rapid growth of anti-obesity drug market. RESEARCH & DEVELOPMENT. 2 Nov 11K16 No. 1061
[2]. Shashoua VE, et al. N-docosahexaenoyl, 3 hydroxytyramine: a dopaminergic compound that penetrates the blood-brain barrier and suppresses appetite. Life Sci. 1996;58(16):1347-57. [3]. Wang Y, et al. N-Docosahexaenoyl Dopamine, an Endocannabinoid-like Conjugate of Dopamine and the n-3 Fatty Acid Docosahexaenoic Acid, Attenuates Lipopolysaccharide-Induced Activation of Microglia and Macrophages via COX-2. ACS Chem Neurosci. 2017 Mar 15;8 |
| Additional Infomation |
NMI 8739 (N-Docosahexaenoyl Dopamine, DHA-DA) is a novel small molecule designed as a dopamine D2 autoreceptor agonist. It is an amine conjugate of the omega-3 fatty acid docosahexaenoic acid (DHA) and dopamine. NMI 8739 reduces nitric oxide production and causes concentration-dependent inhibition of CCL-20, MCP-1, and IL-6 release. The compound has potential applications in Parkinson's disease, schizophrenia, and other neuropsychiatric disorders. Its molecular formula is C30H41NO3. NMI 8739 has not entered clinical trials and has not received regulatory approval. It is available from research chemical suppliers for non-clinical research purposes only. NMI 8739 is a valuable research tool for studying dopamine signaling and neuroinflammation.
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| Molecular Formula |
C30H41NO3
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| Molecular Weight |
463.65144
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| Exact Mass |
463.309
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| CAS # |
129024-87-9
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| PubChem CID |
6443994
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
8.074
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
34
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| Complexity |
687
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCC(NCCC1=CC=C(O)C(O)=C1)=O
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| InChi Key |
HXJMZRVSTICUKC-KUBAVDMBSA-N
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| InChi Code |
InChI=1S/C30H41NO3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-30(34)31-25-24-27-22-23-28(32)29(33)26-27/h3-4,6-7,9-10,12-13,15-16,18-19,22-23,26,32-33H,2,5,8,11,14,17,20-21,24-25H2,1H3,(H,31,34)/b4-3-,7-6-,10-9-,13-12-,16-15-,19-18-
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| Chemical Name |
(4Z,7Z,10Z,13Z,16Z,19Z)-N-[2-(3,4-dihydroxyphenyl)ethyl]docosa-4,7,10,13,16,19-hexaenamide
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
Ethanol : ~100 mg/mL (~215.68 mM)
DMSO : ~65 mg/mL (~140.19 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.39 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 25.0 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: ≥ 2.5 mg/mL (5.39 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 25.0 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 | 2.1568 mL | 10.7840 mL | 21.5680 mL | |
| 5 mM | 0.4314 mL | 2.1568 mL | 4.3136 mL | |
| 10 mM | 0.2157 mL | 1.0784 mL | 2.1568 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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