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| Targets |
Nelotanserin targets serotonin 5-HT₂A, 5-HT₂C, and 5-HT₂B receptors. It acts as a full inverse agonist at 5-HT₂A receptors, a partial inverse agonist at 5-HT₂C receptors, and a weak inverse agonist at 5-HT₂B receptors. Inverse agonists stabilize the receptor in an inactive conformation, reducing constitutive receptor activity. By targeting 5-HT₂A receptors, Nelotanserin modulates serotonergic signaling. The compound shows high potency at 5-HT₂A with an IC₅₀ of 1.7 nM.
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| ln Vitro |
According to the results of the IP accumulation assay, elotanserin is a mild 5-HT2B inverse agonist (IC50=791 nM), a moderately effective 5-HT2C partial inverse agonist (IC50=79 nM) (highest response: 62%) and a potent 5-HT2A full inverse agonist (IC50=1.7 nM). Nelotanserin exhibits medium affinity for the human 5-HT2C receptor (Ki=100 nM), high affinity for the human 5-HT2B receptor that is stable expressed in HEK293 cells, and high affinity for the recombinant human 5-HT2A receptor (Ki=0.35 nM). (2000 nM) exhibited little cell affinity. According to the findings, nerotranserin has a 262-fold higher affinity for the human 5-HT2A receptor than the 5-HT2C receptor and a 6610-fold higher affinity for the human 5-HT2A receptor than the 5-HT2B receptor [1].
In vitro, Nelotanserin potently inhibits 5-HT₂A receptor with an IC₅₀ of 1.7 nM, 5-HT₂C with an IC₅₀ of 79 nM, and 5-HT₂B with an IC₅₀ of 791 nM. It acts as a full inverse agonist at 5-HT₂A and partial inverse agonist at 5-HT₂C. The compound is a powerful and selective 5-HT2A inverse agonist. Detailed in vitro data are available in the primary literature. |
| ln Vivo |
At least five rats were used for each compound's oral gavage test, which was administered six hours after the light exposure started, in the midst of the inactive phase. There were substantial differences in delta power across all evaluated analogs and vehicle controls during non-rapid eye movement sleep (NREMS). The incremental power was greatly boosted by nerotranserin (Compound 39) and remained stable for the first four hours following delivery. However, the length of each NREMS bout varied significantly. Nelotanserin exhibited a considerable increase in NREMS start time within the first hour of treatment. This impact was also observed in the second hour of administration. Nilotanserin (p<0.01) and Compound 15 (p<0.05) [2] decreased the number of NREM episodes within the first hour when combined with an increase in the duration of NREM episodes.
In vivo, Nelotanserin has been used in clinical trials studying the treatment of Lewy Body Dementia, Visual Hallucinations, Dementia With Lewy Bodies, and REM Sleep Behavior Disorder. The compound's 5-HT₂A inverse agonism is relevant for psychiatric and neurological disorders. Further in vivo studies are needed to fully characterize its efficacy and safety profile. The compound is a research tool for serotonin receptor studies. |
| Enzyme Assay |
In vitro receptor binding and functional assays for Nelotanserin typically use membrane preparations from cells expressing human serotonin receptors (5-HT₂A, 5-HT₂C, 5-HT₂B). Radioligand binding is performed using [³H]-ketanserin (5-HT₂A) or [³H]-mesulergine (5-HT₂C) as tracers. Membranes are incubated with radioligand and varying concentrations of Nelotanserin in assay buffer at room temperature for 60-90 minutes. Nonspecific binding is determined using excess unlabeled ligand. Bound radioactivity is measured by filtration and scintillation counting. IC₅₀ and Ki values are calculated from competition curves. Functional assays measure serotonin-induced calcium mobilization to determine inverse agonist activity.
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| Cell Assay |
For cell-based assays, cells expressing serotonin receptors (e.g., CHO or HEK-293 transfectants) are cultured in DMEM with 10% FBS and selection antibiotics. Cells are seeded in 96-well plates and loaded with calcium-sensitive dye. Cells are treated with Nelotanserin at various concentrations (0.001-10 μM) and calcium flux is measured. Inverse agonist activity is assessed by measuring baseline receptor activity in the absence of agonist. IC₅₀ values are calculated from dose-response curves. Cell viability is assessed by standard assays. All treatments include vehicle controls and are performed in triplicate.
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| Animal Protocol |
In vivo, Nelotanserin has been evaluated in clinical trials. For animal studies, rodents are dosed orally or via other routes. Behavioral studies in models of psychosis, dementia, and sleep disorders are performed. Endpoints include behavioral assessments, EEG monitoring, and biomarker analysis. Blood samples are collected for pharmacokinetic analysis. All procedures follow institutional guidelines.
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| ADME/Pharmacokinetics |
Nelotanserin (MW 437.24, C₁₈H₁₅BrF₂N₄O₂) is a 5-HT₂A inverse agonist with an IC₅₀ of 1.7 nM. The compound is soluble in DMSO. Detailed pharmacokinetic parameters (bioavailability, half-life, clearance) are available from clinical trial data. The compound has been evaluated in Phase 2 clinical trials. It is typically stored at -20°C. The compound is for research purposes.
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| Toxicity/Toxicokinetics |
Toxicology data for Nelotanserin are available from clinical trial data. As a serotonin receptor inverse agonist, potential effects on serotonergic signaling should be considered. The compound has been evaluated in Phase 2 clinical trials for Lewy Body Dementia and related conditions. Standard safety pharmacology and toxicology studies have been conducted as part of clinical development. The compound is for research use only and not approved for clinical use.
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| References |
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| Additional Infomation |
Nelotanserin belongs to the pyrazole class of compounds and is a cyclic compound. Nelotanserin has been used in clinical trials for the treatment of Lewy body dementia, visual hallucinations, and REM sleep behavior disorder. It is a highly selective 5-HT2A serotonin receptor antagonist. It increases non-REM sleep (the most restorative stage of the sleep cycle) without affecting REM sleep or dream sleep. Nelotanserin's mechanism of action differs from currently marketed drugs. Nelotanserin potently and selectively targets the 5-HT2A serotonin receptor, blocking excitatory pathways in the central nervous system. This mechanism is not expected to produce the side effects of GABA-A drugs.
Nelotanserin is a research-grade 5-HT₂A inverse agonist studied for the treatment of Lewy Body Dementia, Visual Hallucinations, Dementia With Lewy Bodies, and REM Sleep Behavior Disorder. It has been evaluated in Phase 2 clinical trials. The compound is not approved for clinical use. It is commercially available from various chemical suppliers for research purposes only. Its mechanism involves potent inverse agonism at 5-HT₂A receptors. |
| Molecular Formula |
C18H15BRF2N4O2
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|---|---|
| Molecular Weight |
437.2448
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| Exact Mass |
436.035
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| CAS # |
839713-36-9
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| PubChem CID |
11683556
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| Appearance |
White to off-white solid powder
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| Density |
1.55 g/cm3
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| Boiling Point |
425.886ºC at 760 mmHg
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| Flash Point |
211.369ºC
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| LogP |
4.867
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
518
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
COSPVUFTLGQDQL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H15BrF2N4O2/c1-25-17(13(19)9-22-25)12-8-11(4-6-16(12)27-2)23-18(26)24-15-5-3-10(20)7-14(15)21/h3-9H,1-2H3,(H2,23,24,26)
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| Chemical Name |
1-[3-(4-bromo-2-methylpyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea
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| Synonyms |
APD 125; APD-125; APD125
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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 : ≥ 32 mg/mL (~73.19 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2871 mL | 11.4354 mL | 22.8707 mL | |
| 5 mM | 0.4574 mL | 2.2871 mL | 4.5741 mL | |
| 10 mM | 0.2287 mL | 1.1435 mL | 2.2871 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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