ホームページ Neuronal Signaling 5-HT Receptor antagonist RS-127445 For research use only.

RS-127445

別名：MT500

RS-127445 (MT500) is a selective 5-HT2B receptor antagonist with pKi of 9.5 and pIC50 of 10.4, exhibits >1000-fold selectivity against other 5-HT receptors.

RS-127445化学構造

CAS No. 199864-87-4

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製品安全説明書

現在のバッチを見る： S269801 DMSO] 56 mg/mL] false] Ethanol] 8 mg/mL] false] Water] Insoluble] false 純度： 98.72%
98.72

RS-127445関連製品

シグナル伝達経路

5-HT Receptor Signaling Pathways

5-HT Receptorシグナル伝達経路

5-HT Receptor阻害剤の選択性比較

生物活性

製品説明 RS-127445 (MT500) is a selective 5-HT2B receptor antagonist with pKi of 9.5 and pIC50 of 10.4, exhibits >1000-fold selectivity against other 5-HT receptors.
Targets
5-HT2B [1] 5-HT2B [1]
10.4(pIC50) 9.5(pKi)
In Vitro
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. [1]
Kinase Assay Radioligand binding
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 3×10 5 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.
細胞実験 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]
In Vivo
In Vivo RS-127445 is readily absorbed with no obvious dose or route-dependent limitations and rapidly absorbed following both oral and intraperitoneal administration with peak plasma concentrations being achieved within 15 min of dosing. This compound's concentration in the plasma are proportional to the administered dose. When administered at a dose of 5 mg/kg with approximately 60% of an intraperitoneal dose and 14% of the oral dose is bioavailable. Its concentration in the plasma is predicted to fully saturate accessible 5-HT2B receptors can be readily achieved and maintained in the rat. This chemical administered at 1 to 10 mg/kg with oral significantly inhibits visceral hypersensitivity up to 35 to 74% provoked by restraint stress. Oral administration produces a significant suppression of TNBS-induced visceral hypersensitivity (15 to 62% inhibition at 3 to 30 mg/ kg), although it has no significant effect on the visceral nociceptive threshold of native rats. It administrated orally with 1 to 30 mg/kg also dose -dependently reduce the restraint stress-induced defecation in native and TNBS-treated rats. [2]. This compound inhibits colonic motility and defecation. [3]
動物実験 動物モデル rats
投与量 5 mg/kg
投与経路 Oral for 2.5 h ,intraperitoneal and intravenousroutes for 0.08 h
  • https://pubmed.ncbi.nlm.nih.gov/10455251/
  • http://www.ncbi.nlm.nih.gov/pubmed/ 19740115
  • https://pubmed.ncbi.nlm.nih.gov/19371340/

化学情報

分子量 281.33 化学式

C17H16FN3
CAS No. 199864-87-4 SDF Download RS-127445 SDFをダウンロードする
Smiles CC(C)C1=NC(=NC(=C1)C2=CC=C(C3=CC=CC=C32)F)N
保管

In vitro
Batch:

DMSO : 56 mg/mL ( (199.05 mM)； 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 8 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

mg/kg g μL 匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH2O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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