RS-127445

製品コードS2698 バッチS269801

印刷

化学情報

Synonyms

MT500

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₇H₁₆FN₃

分子量

281.33

CAS No.

199864-87-4

Solubility (25°C)*

体外

DMSO

56 mg/mL (199.05 mM)

Ethanol

8 mg/mL (28.43 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.800mg/ml (9.95mM)	Taking the 1 mL working solution as an example, add 50 μL of 56 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	2%DMSO 1 30%PEG300 2 5%TWEEN80 3 63%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.000mg/ml (3.55mM)	Taking the 1 mL working solution as an example, add 20 μL of 50 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 630 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	RS-127445 (MT500) は、pK_iが9.5、pIC50が10.4である選択的な5-HT2B受容体拮抗薬であり、他の5-HT Receptorに対して1000倍を超える選択性を示します。
in vitro	RS-127445 is a novel high affinity, selective 5-HT2B receptor antagonist devoid of detectable intrinsic activity. This compound is found to have nM affinity and 1000 fold selectivity for the 5-HT2B receptor. It is thus among the highest affinity, most selective 5- HT2B receptor ligands. This chemical potently blocks the 5-HT evoked increase in inositol phosphate formation and blocks the 5-HT evoked increases in intracellular calcium concentrations with a potency 1000 times greater than that of yohimbine.
in vivo	LD50: Mice 391.4mg/kg (i.v.); Rats 370.1mg/kg (i.v.); Rabbits 142.3mg/kg (i.v.)

プロトコル(参考用のみ)

キナーゼアッセイ	Radioligand binding
キナーゼアッセイ	The selectivity of RS-127445 for 5-HT2B receptors is examined by testing this compound for affinity at over 100 additional ion channel or receptor binding sites. CHO-K1 cells expressing human 5-HT2A, 5-HT2B or 5-HT2C receptors are harvested using 2 mM EDTA in phosphate buffered saline. Cell membranes are prepared by four cycles of homogenization and centrifugation (48,000×g for 15 min). Each assay is established so as to achieve steady state conditions and to optimize specific binding. For the 5-HT2A receptor, membranes from 1×10⁶ cells are incubated with 0.2 nM [³ H]-ketanserin at 32 °C for 60 min. Nonspecific binding is determined using 10 μM methysergide. For the 5-HT2B receptor, membranes from 1.5×10⁶ cells are incubated with 0.2 nM [³ H]-5-HT at 48 °C for 120 min. Nonspecific binding is determined using 10 μM 5-HT. For the 5-HT2Creceptor, membranes from 3×10⁵ cells are incubated with 0.5 nM [³ H]-mesuler -gine at 32 °C for 60 min. Nonspecific binding is determined using 10μM methysergide. Assays are terminated by vacuum filtration through glass fibre filters(GF/B) which has been pretreated with 0.1% polyethyleneimine. Total and bound radioactivity is determined by liquid scintillation counting. Greater than 90% specific binding is achieved in each of these assays.
細胞アッセイ	細胞株	HEK-293 cells expressing the human 5-HT2B receptor
	濃度	10 μM
	反応時間	20 min
	実験の流れ	RS-127445, vehicle or other antagonists are pre-incubated with 240 μl of HEK-293 cells expressing the human 5-HT2B receptor suspension at 37 °C for 20 min. HEK-293 cells are incubated with[3H]-myoinositol (1.67 μCi/ml) in 162 cm² flasks overnight at 37 °C in an inositol free Ham's F12 medium containing 10% dialyzed foetal bovine serum. The cells are harvested, washed five times with phosphate bufffered saline and resuspended in inositol free Ham's F12 media at density of approximately 3×10³ cells/ml. The reactions are initiated by addition of 5-HT. Sixty minutes later, the reactions are terminated by adding 50 μl of ice-cold 20% perchloric acid, chilled in an ice-water bath for 10 min and then neutralized with 160μl of 1 N KOH. Each sample is diluted with 2 ml of 50 mM Tris-HCl, pH 7.4 at room temperature. The aqueous portion (2.2 ml) is transferred onto Dowex AG1X8 columns (1 ml, 1 : 1, w/v) which has been washed with 5 ml of distilled water. The columns are then washed with 18 ml of distilled water and the inositol phosphates are eluted with 3 ml of 1 N HCl. The eluted radioactivity is determined by liquid scintillation spectroscopy using a Packard 1900CA analyzer. ^[1]
動物実験	動物モデル	rats
	投薬量	5 mg/kg
	投与方法	Oral for 2.5 h ,intraperitoneal and intravenousroutes for 0.08 h

参考

https://pubmed.ncbi.nlm.nih.gov/10455251/
http://www.ncbi.nlm.nih.gov/pubmed/ 19740115
https://pubmed.ncbi.nlm.nih.gov/19371340/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Fluoxetine inhibited the activation of A1 reactive astrocyte in a mouse model of major depressive disorder through astrocytic 5-HT2BR/β-arrestin2 pathway [ J Neuroinflammation, 2022, 19(1):23]	PubMed: 35093099
Serotonin-induced vascular permeability is mediated by transient receptor potential vanilloid 4 in the airways and upper gastrointestinal tract of mice [ Lab Invest, 2021, 1-14]	PubMed: 33859334
Serotonin receptors 5-HTR2A and 5-HTR2B are involved in cigarette smoke-induced airway inflammation, mucus hypersecretion and airway remodeling in mice. [ Int Immunopharmacol, 2019, 10.1016/j.intimp.2019.106036]	PubMed: 31787571
α2- and β2-Adrenoreceptor-Mediated Efficacy of the Atypical Antidepressant Agomelatine Combined With Gabapentin to Suppress Allodynia in Neuropathic Rats With Ligated Infraorbital or Sciatic Nerve [M'Dahoma S, et al. Front Pharmacol, 2018, 9:587]	PubMed: 29930510

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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