| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
5-HT2C receptor (pKi = 9.14 ± 0.07, n=16) [2]
5-HT2B receptor (pKi = 8.14 ± 0.08, n=14) [2] 5-HT2A receptor (pKi = 6.97 ± 0.06, n=16) [2] |
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| ln Vitro |
SB-228357 (compound 32) exhibited excellent 5-HT2C receptor binding affinity with pKi = 9.0 (from Table 3), 100-fold selectivity over 5-HT2A (pKi = 6.9) and 10-fold selectivity over 5-HT2B (pKi = 8.0) in radioligand binding studies using human cloned receptors expressed in HEK293 cells. [1]
In a 5-HT-stimulated phosphoinositide hydrolysis model using human cloned 5-HT2C receptors expressed in HEK293 cells, SB-228357 displayed negative efficacy (inverse agonist) with a pKB of 9.3, completely abolishing the basal effector activity characteristic of this cloned system. [1] SB-228357 demonstrated low inhibition of human CYP1A2 (IC50 > 100 μM), CYP2C9 (IC50 = 28 μM), CYP2C19 (IC50 = 2 μM), and CYP2D6 (IC50 > 100 μM), with an IC50 of 8 μM for CYP3A4. [1] On cross-screening, SB-228357 was found to have >100-fold selectivity over more than 50 other receptor, ion-channel, and enzyme binding sites. [1] |
| ln Vivo |
Haloperidol-induced catalepsy was dramatically reversed in male Sprague Dawley rats after 90 minutes of oral SB228357 treatment (0–10 mg/kg) [2].
SB-228357 (0.32–10 mg/kg p.o.) significantly attenuated haloperidol-induced catalepsy in rats. At 10 mg/kg, catalepsy was observed in only 1 out of 6 rats (P < 0.01) compared to haloperidol alone. The effect was dose-dependent, and the compound showed a pronounced anticataleptic profile. [2] |
| Enzyme Assay |
Radioligand binding assays were performed with homogenates of human recombinant 5-HT2A, 5-HT2B, and 5-HT2C receptors expressed in HEK293 cells. Washed membranes were incubated with ten concentrations (1×10⁻¹¹ M to 1×10⁻⁵ M) of test compounds and 0.5 nM [³H]-ketanserin (for 5-HT2A), 8 nM [³H]-5-HT (for 5-HT2B), or 0.6 nM [³H]-mesulergine (for 5-HT2C) for 30–45 min at 37°C in a pH 7.4 50 mM Tris buffer. Ki values were calculated from IC50 values using the Cheng-Prusoff equation with KD values of 0.7 nM (5-HT2A), 11.0 nM (5-HT2B), and 0.58 nM (5-HT2C). pKi values were calculated as the negative logarithm of the molar Ki. [2]
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| Cell Assay |
In a 5-HT-stimulated phosphoinositide hydrolysis model of 5-HT2C receptor function, using human cloned receptors expressed in HEK293 cells, SB-228357 was found to display negative efficacy (inverse agonist) with a pKB of 9.3, completely abolishing the basal effector activity characteristic of this cloned system. [1]
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| Animal Protocol |
Animal/Disease Models: Male Sprague Dawley rats (200-250 g) injected with haloperidol [2]
Doses: 0 mg/kg, 0.32 mg/kg, 1 mg/kg, 3.2 mg/kg, 10 mg/kg Route of Administration: Oral administration; Mode of Route of Administration: Oral administration. 90-minute Experimental Results: Significant reversal of haloperidol-induced catalepsy. Male Sprague Dawley rats (200–250 g) were housed in groups of six under a 12 h light/dark cycle with free access to food and water. For catalepsy testing, rats were positioned with hindquarters on the bench and forelimbs resting on a 1 cm diameter horizontal bar, 10 cm above the bench. The time the rats maintained this position was recorded by stopwatch to a maximum of 120 s at 30, 60, and 90 min after drug administration. Rats were judged cataleptic (score = 1) if they maintained the position for ≥30 s; otherwise score = 0. SB-228357 (0.32–10 mg/kg) was ground in one drop of BRIJ-35 and diluted in 1% methylcellulose, then administered orally at 2 ml/kg. Haloperidol (1.13 mg/kg) was dissolved with an equal weight of tartaric acid and injected intraperitoneally at 1 ml/kg immediately after the 5-HT2 receptor antagonists. Each treatment group consisted of six rats, and the assessor was blind to the treatments. Data at the 90 min time point were analyzed using logistic regression in SAS. [2] |
| Toxicity/Toxicokinetics |
SB-228357 showed significantly reduced cytochrome P450 inhibitory liability compared to earlier compound 2. CYP1A2 inhibition: IC50 > 100 μM (vs 0.013 μM for compound 2); CYP2C9: IC50 = 28 μM (vs >100 μM for compound 2); CYP2C19: IC50 = 2 μM (vs >100 μM for compound 2); CYP2D6: IC50 > 100 μM (vs 0.11 μM for compound 2); CYP3A4: IC50 = 8 μM (vs >100 μM for compound 2). [1]
Acute administration showed no evidence of proconvulsant activity in the rat maximal electroshock threshold test (up to 30 mg/kg p.o.). [1] Chronic administration (up to 30 mg/kg p.o. × 14 days) produced no evidence of hyperphagic properties. [1] No evidence of increased sensitivity to 5-HT2C agonist-induced effects after chronic dosing, indicating no effects on receptor density or sensitivity. [1] |
| References |
[1]. Bromidge SM, et al. Biarylcarbamoylindolines are novel and selective 5-HT(2C) receptor inverse agonists: identification of 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]- 5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/a
[2]. Reavill C, et al. Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist. Br J Pharmacol. 1999 Feb;126(3):572-4. |
| Additional Infomation |
SB 228357 is an indole carboxylic acid.
SB-228357 is a selective 5-HT2C/2B receptor antagonist with high affinity for the 5-HT2C receptor (pKi = 9.14) and 100-fold and 10-fold selectivity over 5-HT2A and 5-HT2B receptors, respectively. The compound significantly reversed haloperidol-induced catalepsy, whereas selective 5-HT2A (MDL-100907) and 5-HT2B (SB-215505) antagonists did not, indicating that 5-HT2C receptor antagonism is likely the mechanism by which atypical antipsychotics lack extrapyramidal side-effects. [2] |
| Molecular Formula |
C22H17F4N3O2
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|---|---|
| Molecular Weight |
431.39
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| Exact Mass |
431.126
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| Elemental Analysis |
C, 61.25; H, 3.97; F, 17.62; N, 9.74; O, 7.42
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| CAS # |
181629-93-6
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| PubChem CID |
443390
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| Appearance |
Solid powder
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| Density |
1.398g/cm3
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| Boiling Point |
625.4ºC at 760mmHg
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| Flash Point |
332ºC
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| Vapour Pressure |
1.48E-15mmHg at 25°C
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| Index of Refraction |
1.599
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| LogP |
5.647
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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 |
3
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| Heavy Atom Count |
31
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| Complexity |
634
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RRJLJKRFFRZRAF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H17F4N3O2/c1-31-20-9-13-4-6-29(19(13)11-18(20)22(24,25)26)21(30)28-17-8-15(7-16(23)10-17)14-3-2-5-27-12-14/h2-3,5,7-12H,4,6H2,1H3,(H,28,30)
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| Chemical Name |
N-(3-fluoro-5-pyridin-3-ylphenyl)-5-methoxy-6-(trifluoromethyl)-2,3-dihydroindole-1-carboxamide
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| Synonyms |
SB 228357 SB228357SB-228357
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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 : ~125 mg/mL (~289.77 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 | 2.3181 mL | 11.5904 mL | 23.1809 mL | |
| 5 mM | 0.4636 mL | 2.3181 mL | 4.6362 mL | |
| 10 mM | 0.2318 mL | 1.1590 mL | 2.3181 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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