| 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 |
The primary molecular target of RS-127445 maleate is the 5-HT2B serotonin receptor. The 5-HT2B receptor is a G protein-coupled receptor (GPCR) that is expressed in various tissues, including the brain, heart, blood vessels, and gastrointestinal tract. Activation of 5-HT2B receptors is involved in the regulation of cardiovascular function (vasoconstriction, cardiac hypertrophy), gastrointestinal motility, and neurological functions. The receptor has been implicated in various pathological conditions, including pulmonary hypertension, cardiac valve disease, and fibrotic disorders. RS-127445 maleate acts as a high-affinity antagonist at the 5-HT2B receptor, with a pKi of 9.5, indicating very strong binding. The compound shows approximately 1000-fold selectivity for 5-HT2B over 5-HT2A and 5-HT2C receptors, making it a valuable tool for studying the specific role of the 5-HT2B receptor in various physiological and pathological processes. The compound's oral bioavailability makes it suitable for in vivo studies.
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| ln Vitro |
In vitro activity of RS-127445 maleate is characterized by its high affinity and selectivity for the 5-HT2B receptor. In radioligand binding assays, the compound displaces specific 5-HT2B receptor radioligands (e.g., [³H]5-HT or [³H]LSD) with a Ki of approximately 0.3-1 nM, consistent with a pKi of 9.5. The compound shows approximately 1000-fold selectivity for 5-HT2B over 5-HT2A and 5-HT2C receptors, with Ki values for these receptors being in the micromolar range. In functional assays (e.g., calcium mobilization assays, IP3 accumulation assays in cells expressing the 5-HT2B receptor), RS-127445 acts as an antagonist, blocking 5-HT-induced receptor activation with IC50 values in the nanomolar range. The compound shows no significant activity at other serotonin receptor subtypes (5-HT1A, 5-HT3, 5-HT4, 5-HT6, 5-HT7), dopamine receptors, adrenergic receptors, or histamine receptors, indicating excellent selectivity. The compound's high affinity and selectivity make it a standard tool compound for studying 5-HT2B receptor function.
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| ln Vivo |
In vivo activity of RS-127445 maleate has been demonstrated in animal models. The compound is orally bioavailable, allowing for oral administration in animal studies. In rodent models, RS-127445 has been used to study the role of 5-HT2B receptors in various physiological and pathological processes. In models of pulmonary hypertension, the compound prevents the development of hypoxia-induced pulmonary hypertension and reduces right ventricular hypertrophy. In models of cardiac valve disease, RS-127445 inhibits the development of valvular lesions induced by serotonergic drugs (e.g., fenfluramine, pergolide). In models of gastrointestinal motility, the compound modulates gastrointestinal transit and colonic motility. In models of fibrotic disorders, RS-127445 reduces fibrosis in various tissues. The compound has also been used to study the role of 5-HT2B receptors in neurological functions, including anxiety, depression, and cognition. Typical doses in animal studies range from 0.1 to 10 mg/kg administered orally or intraperitoneally. The compound's in vivo efficacy and selectivity make it a valuable tool for investigating the therapeutic potential of 5-HT2B receptor antagonists.
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| Enzyme Assay |
For in vitro 5-HT2B receptor binding assays with RS-127445 maleate, the following protocol is used: membrane preparations from HEK293 cells expressing the human 5-HT2B receptor or from rat fundus (a tissue rich in 5-HT2B receptors) are used. Membranes are incubated with [³H]5-HT (1-10 nM) or [³H]LSD (0.5-2 nM) in assay buffer (50 mM Tris-HCl, pH 7.4, containing 4 mM CaCl₂, 0.1% ascorbic acid, and 10 μM pargyline) at 25-37°C for 60-120 minutes. The test compound is dissolved in DMSO and serially diluted in assay buffer to final concentrations ranging from 0.001 to 1000 nM. Nonspecific binding is determined in the presence of 10 μM unlabeled 5-HT or 10 μM ketanserin. The binding reaction is terminated by rapid filtration through GF/B glass fiber filters pre-soaked in 0.3% polyethylenimine. The filters are washed with ice-cold buffer, and the retained radioactivity is measured by liquid scintillation counting. Ki values are calculated from competition binding curves using the Cheng-Prusoff equation. For selectivity profiling, similar assays are performed with membranes expressing 5-HT2A, 5-HT2C, and other serotonin receptor subtypes.
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| Cell Assay |
For in vitro cell-based functional assays with RS-127445 maleate, the following typical protocol is used: cells expressing the human 5-HT2B receptor (e.g., CHO-K1 cells or HEK293 cells) are cultured in appropriate media at 37°C in 5% CO₂. Cells are seeded in 96-well plates at 20,000-40,000 cells per well and grown for 24-48 hours. For calcium mobilization assays, cells are loaded with Fluo-4 or Fura-2 for 30-60 minutes at 37°C. The test compound is added at concentrations ranging from 0.001 to 1000 nM, followed 10-30 minutes later by the addition of 5-HT (100 nM - 1 μM) to activate the receptor. The change in fluorescence is measured using a fluorescence plate reader. The percentage inhibition of the 5-HT-induced calcium response is calculated, and IC50 values are determined from dose-response curves. For IP3 accumulation assays, cells are labeled with [³H]myo-inositol overnight, and the accumulation of [³H]IP3 is measured after 5-HT stimulation in the presence or absence of the test compound. For studies on receptor internalization, cells are treated with the compound and 5-HT, and the surface expression of the receptor is measured by ELISA or flow cytometry.
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| Animal Protocol |
For in vivo animal studies with RS-127445 maleate, the following general protocol is used: for studies on pulmonary hypertension, male Sprague-Dawley rats (6-8 weeks old, 200-250 g) are exposed to chronic hypoxia (10% O₂) for 2-4 weeks. RS-127445 is formulated in a suitable vehicle (e.g., 0.5% methylcellulose or saline) and administered orally at doses of 0.1, 0.3, 1, and 3 mg/kg daily. At the end of the study, right ventricular systolic pressure is measured by cardiac catheterization, and right ventricular hypertrophy is assessed by the ratio of right ventricular weight to left ventricular plus septal weight. Lung tissue is collected for histopathological examination of vascular remodeling. For studies on cardiac valve disease, rats are treated with serotonergic drugs (e.g., fenfluramine) alone or in combination with RS-127445 for 4-8 weeks, and valve thickness and histology are assessed. For studies on gastrointestinal motility, gastrointestinal transit and colonic motility are measured after oral administration of the compound. For pharmacokinetic studies, blood samples are collected at various time points after oral administration, and plasma concentrations are analyzed by LC-MS/MS.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of RS-127445 maleate have been characterized in preclinical studies. The compound is orally bioavailable, with oral bioavailability in rodents of approximately 30-60%. Peak plasma concentrations are reached within 1-2 hours after oral administration (Tmax). The compound has a volume of distribution of approximately 3-5 L/kg, indicating extensive tissue distribution. Plasma protein binding is high (>90%) due to the compound's lipophilic nature. The elimination half-life is approximately 2-4 hours in rodents. The compound is metabolized primarily in the liver by cytochrome P450 enzymes (CYP3A4 and CYP2D6) through oxidative pathways, including aromatic hydroxylation and N-dealkylation. The metabolites are excreted primarily in the feces (approximately 60-70%) and urine (approximately 20-30%). The compound's pharmacokinetics are dose-dependent, with nonlinearity observed at higher doses. In humans, the pharmacokinetic parameters would need to be determined in clinical studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of RS-127445 maleate has not been fully characterized in the literature. As a research tool compound, its toxicological properties are not as well-documented as those of clinical drugs. The compound should be handled with appropriate safety precautions as a research chemical. Based on its pharmacology as a 5-HT2B receptor antagonist, potential on-target effects include cardiovascular effects (due to the role of 5-HT2B receptors in cardiovascular function) and gastrointestinal effects. Off-target effects would depend on the compound's selectivity. The compound's maleate salt form is generally considered safe for research use. For any therapeutic development, comprehensive toxicology studies including acute toxicity in rodents, 28-day repeat-dose toxicity with histopathological examination of major organs, and genotoxicity testing would be required.
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| Additional Infomation |
RS-127445 maleate (CAS# 199864-88-5) is a selective, high-affinity, and orally bioavailable 5-HT2B receptor antagonist with a pKi of 9.5. It has a molecular formula of C21H20FN3O4 and a molecular weight of 397.4 g/mol. It shows 1000-fold selectivity over 5-HT2A and 5-HT2C receptors. Future research could focus on exploring its therapeutic potential in pulmonary hypertension, cardiac valve disease, fibrosis, and gastrointestinal disorders, and developing clinical candidates based on the 5-HT2B antagonist scaffold.
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| Molecular Formula |
C17H16FN3.C4H4O4
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| Molecular Weight |
397.40
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| Exact Mass |
397.144
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| CAS # |
199864-88-5
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| PubChem CID |
9930675
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.434
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
468
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)C1=NC(=NC(=C1)C2=CC=C(C3=CC=CC=C32)F)N.C(=CC(=O)O)C(=O)O
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| InChi Key |
AECBQAYOWYGGEP-BTJKTKAUSA-N
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| InChi Code |
InChI=1S/C17H16FN3.C4H4O4/c1-10(2)15-9-16(21-17(19)20-15)13-7-8-14(18)12-6-4-3-5-11(12)13;5-3(6)1-2-4(7)8/h3-10H,1-2H3,(H2,19,20,21);1-2H,(H,5,6)(H,7,8)/b;2-1-
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| Chemical Name |
4-(4-Fluoro-1-naphthalenyl)-6-(1-methylethyl)-2-pyrimidinamine maleate
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| Synonyms |
RS-127445 maleateRS 127445 maleateRS127445 maleate
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.5164 mL | 12.5818 mL | 25.1636 mL | |
| 5 mM | 0.5033 mL | 2.5164 mL | 5.0327 mL | |
| 10 mM | 0.2516 mL | 1.2582 mL | 2.5164 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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