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| 25mg |
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SB 204741 (SB-204741) is a novel and potent 5-HT2B receptor antagonist with the potential for treating and preventingpulmonary arterial hypertension (PAH) and vascular stiffness.
| Targets |
5-HT2B Receptor (pKi = 7.1)
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|---|---|
| ln Vitro |
In comparison to the human 5-HT2C receptor, SB 204741 exhibits selectivity for the human 5-HT2B receptor that is about 20 times greater than that of any other 5-HT2B receptor ligand that needs to be tested[1].
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| ln Vivo |
After isoproterenol-induced myocardial damage, SB-204741 (0.25~1.0 mg/kg; ip) causes myocardial remodeling and improves hemodynamic and ventricular functions in a dose-dependent manner[1]. In rats undergoing isoproterenol-induced myocardial remodeling, SB-204741 increases the activities of endogenous antioxidant enzymes, enhances heart damage indicators, NO level, and lipid peroxidation level, and reduces TNFα level. After isoproterenol-induced cardiac remodeling, pre-treatment with SB-204741 (0.5 and 1.0 mg/kg/day) for 28 days significantly increases NO level, GSH and SOD activities, and attenuates TBARS level. In rats undergoing isoproterenol-induced cardiac remodeling, SB-204741 suppresses the expression of inflammatory proteins, increases autophagy, and increases the expression of HSPs proteins. Rats are the model[1]. The dose is 0.25–1.0 mg/kg. Management: Ip Result: Remodeling of the heart was induced.
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| Enzyme Assay |
1. Full length clones of the human 5-HT2B receptor were isolated from human liver, kidney and pancreas. The cloned human 5-HT2B receptors had a high degree of homology (approximately 80%) with the rat and mouse 5-HT2B receptors. 2. PCR amplification was used to determine the tissue distribution of human 5-HT2B receptor mRNA. mRNA encoding the 5-HT2B receptor was expressed with greatest abundance in human liver and kidney. Lower levels of expression were detected in cerebral cortex, whole brain, pancreas and spleen. Expression was not detected in heart. 3. Northern blot analysis confirmed the presence of 5-HT2B receptor mRNA (a 2.4 kB sized band) in pancreas, liver and kidney. An additional 3.2 kB sized band of hybridization was detected in liver and kidney. This raises the possibility of a splice variant of the receptor or the presence of an additional homologous receptor. 4. The human 5-HT2B receptor was expressed in Cos-7 cells and its ligand binding characteristics were compared to similarly expressed human 5-HT2A and 5-HT2C receptors. The ligand specificity of the human 5-HT2B receptor (5-HT > ritanserin > SB 204741 > spiperone) was distinct from that of the human 5-HT2A (ritanserin > spiperone > 5-HT > SB 204741) and 5-HT2C (ritanserin > 5-HT > spiperone = SB 204741) receptors. On the basis of a higher affinity for ketanserin and a lower affinity for yohimbine the human 5-HT2B receptor also appeared to differ from the rat 5-HT2B receptor. 5. These findings confirm the sequence of the human 5-HT2B receptor and they demonstrate that the receptor has a widespread tissue distribution. In addition, these data suggest that there are differences in ligand affinities between different species homologues of the receptor. Finally, the finding of two distinct bands on the Northern blots of liver and kidney raises the possibility of splice variants or subtypes of 5-HT2B receptors, within these tissues. [1]
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| Animal Protocol |
In the present study, researchers sought to investigate the role of SB-204741, a 5-HT2BR blocker in isoproterenol-induced myocardial remodeling in rats and its cross-talk with apoptosis and mitogen activated protein kinase (MAPKs)/heat shock proteins (HSPs) pathway. To assess this hypothesis, researchers measured the effect of SB-204741 (0.25-1.0 mg/kg/day, i.p.) in isoproterenol (85 mg/kg/day, s.c.)-induced myocardial remodeling in rats. SB-204741 dose dependently improved hemodynamic and ventricular functions following isoproterenol-induced myocardial injury. This amelioration was well substantiated with reduced expression of 5-HT2B, inflammatory proteins (NF-κBp65, IKK-β, TNF-α, IL-6, and Cox-2), MAPKs (p-p38/p38 and p-JNK/JNK ratio) accompanied with increased protein expression of HSPs (αB-crystallin, Hsp27 and Hsp70), autophagy (LC3 and Beclin-1) and p-ERK/ERK ratio. Additionally, SB-204741 inhibited apoptotic signaling pathway as there was decreased DAPI/TUNEL positivity and protein expression of cytochrome c, Bax, and caspase-3 along with increased Bcl-2 expression. Preservation of histopathological and ultrastructural components, normalization of nitric oxide level, endogenous antioxidants and myocyte injury marker enzymes were also observed. In conclusion, inhibition of apoptosis via modulation of MAPKs/HSPs is essential for 5-HT2BR blockade mediated cardioprotective effect.
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| References |
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| Additional Infomation |
1-(1-methylindol-5-yl)-3-(3-methyl-1,2-thiazol-5-yl)urea is a member of ther class of ureas that is urea in which a hydrogen attached to one of the nitrogens has been replaced by an N-methylindol-5-yl group, while a hydrogen attached to the other nitrogen has been replaced by a 3-methyl-1,2-thiazol-5-yl group. It is a potent and selective antagonist for the 5-hydroxytryptamine 2B (5-HT2B) receptor. It has a role as a receptor modulator and a serotonergic antagonist. It is a member of ureas, a member of indoles and a member of 1,2-thiazoles.
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| Molecular Formula |
C14H14N4OS
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|---|---|
| Molecular Weight |
286.35
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| Exact Mass |
286.089
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| Elemental Analysis |
C, 58.72; H, 4.93; N, 19.57; O, 5.59; S, 11.20
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| CAS # |
152239-46-8
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| PubChem CID |
3277600
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| Appearance |
White to off-white solid powder
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| Density |
1.38g/cm3
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| Boiling Point |
335.9ºC at 760 mmHg
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| Flash Point |
157ºC
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| Vapour Pressure |
0.000116mmHg at 25°C
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| Index of Refraction |
1.707
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| LogP |
3.733
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
367
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
USFUFHFQWXDVMH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H14N4OS/c1-9-7-13(20-17-9)16-14(19)15-11-3-4-12-10(8-11)5-6-18(12)2/h3-8H,1-2H3,(H2,15,16,19)
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| Chemical Name |
1-(1-methylindol-5-yl)-3-(3-methyl-1,2-thiazol-5-yl)urea
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| Synonyms |
SB 204741; 152239-46-8; SB204741; 1-(1-methylindol-5-yl)-3-(3-methyl-1,2-thiazol-5-yl)urea; SB-204741; 1-(1-methyl-1H-indol-5-yl)-3-(3-methylisothiazol-5-yl)urea; 9VHM49MS42; N-(1-Methyl-1H-5-indolyl)-N'-(3-methyl-5-isothiazolyl)urea;
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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) |
DMSO : ~100 mg/mL (~349.22 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.26 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 20.8 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: ≥ 2.08 mg/mL (7.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4922 mL | 17.4611 mL | 34.9223 mL | |
| 5 mM | 0.6984 mL | 3.4922 mL | 6.9845 mL | |
| 10 mM | 0.3492 mL | 1.7461 mL | 3.4922 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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