Clemastine fumarate

別名：HS-592 fumarate, Meclastine fumarate

製品コード：S1847 純度：99.97%

Clemastine fumarate is a selective histamine H1 receptor antagonist with IC50 of 3 nM. Clemastine stimulates autophagy via mTOR pathway.

CAS No. 14976-57-9

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
50mg	JPY 22000	国内在庫あり
1g	JPY 70500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

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製品安全説明書

現在のバッチを見る：純度： 99.97%

99.97

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シグナル伝達経路

Histamine Receptorシグナル伝達経路

Histamine Receptor阻害剤の選択性比較

生物活性

製品説明

Clemastine fumarate is a selective histamine H1 receptor antagonist with IC50 of 3 nM. Clemastine stimulates autophagy via mTOR pathway.

Targets

mTOR ^[7]	Histamine H1 receptor ^[1]
	3 nM

In Vitro
In vitro	Clemastine Fumarate inhibits histamine induced rise in [Ca²⁺]_i in HL-60 cells with an IC50 of 3 nM as compared with that of chlorpheniramine or diphenhydramine with IC50 values of 20 nM and 100 nM, respectively. ^[1] At concentrations of ≥25 μM, Clemastine Fumarate significantly blocks NK and ADCC reactions of lymphocytes against the human erythroleukemia cell line K562 and human B-lymphoblast cell line SB, respectively. ^[2] Clemastine Fumarate inhibits histamine-induced contraction of guinea pig ileum with an IC50 of 231 nM. ^[3] Clemastine Fumarate potently inhibits the HERG K⁺ channel in a concentration-dependent manner in HEK 293 cells stably expressing HERG channels with an IC50 of 12 nM, which can be attenuated by the Y652A or F656A mutation of HERG. ^[4] Clemastine Fumarate significantly potentiates ATP-induced increase in [Ca²⁺]_i in HEKhP2X7 cells not relying on histamine receptor blockage but on sensitizing P2X7 receptor in a concentration-dependent manner with an EC50 of 10 μM, and increases the IL-1β release from LPS-induced human macrophages. ^[5]
Kinase Assay	Inhibition of [Ca²⁺]_i
Kinase Assay	HL-60 cells are suspended at 1×10⁷ cells/mL in a buffer consisting of 138 mM NaCl, 6 mM KC1, 1 mM MgSO4, 1 mM Na₂HPO₄, 5 mM NaHCO₃, 5.5 mM glucose, and 20 mM HEPES-NaOH, pH 7.4, supplemented with 0.1% (w/v) bovine serum albumin. The dye fura-2/AM is added at a concentration of 4 μM, and cells are incubated for 10 minutes at 37 °C. Thereafter, cells are diluted with the aforementioned buffer to a concentration of 5×10⁶ cells/mL and incubated for 45 minutes at 37 °C. Subsequently, cells are diluted with the aforementioned buffer to a final concentration of 0.5 × 10⁶ cells/mL and centrifuged at 250 g for 10 minutes at 20 °C. Cells are suspended at 1.0 × 10⁶ cells/mL in the aforementioned buffer and kept at 20 °C until measurement. HL-60 cells are used for up to 4 hours after loading with fura-2/AM, and suspended in 2 mL of the aforementioned buffer, using acryl fluorescence cuvettes. HL-60 cells are incubated for 3 minutes at 37 °C, in the presence of 1 mM Ca²⁺ and various concentrations of Clemastine Fumarate, before the addition of histamine (100 μM). Fluorescence is determined at 37 °C, with constant stirring of the cells at 1×10³ rpm, using a Ratio II spectrofluorometer. The basal fluorescence (basal [Ca²⁺]_i) is measured for 1 minute. The basal [Ca²⁺]_i values are subtracted from the corresponding peak [Ca²⁺]_i values, to calculate the increase in [Ca²⁺]_i. The excitation and emission wavelengths are 340 and 500 nm, respectively. The IC50 value is assessed from competitive curve.

In Vivo
In Vivo	Administration of Clemastine Fumarate (5-20 mg/kg) displays significantly inhibitory effect on simultaneously induced zymosan paw oedema and croton oil ear oedema in rats in a dose-dependent manner, with the inhibition of 53.6% and 46.8%, respectively, at the dose of 20 mg/kg, and with ID50 values of 18.0 mg/kg and 20.5 mg/kg, respectively. ^[6] Clemastine Fumarate treatment strongly reduces innate immune responses to Listeria monocytogenes in mice by interfering with the extracellular signal-regulated kinase (ERK)-mediated production of proinflammatory cytokines such as TNF-α and IL-6 surprisingly not dependent on blocking the histamine H1 receptor, leading to significantly higher mortality. ^[7]
動物実験	動物モデル	Male Wistar rats with paw oedema induced by subplantar injection of zymosan and ear oedema induced by croton oil
	投与量	5-20 mg/kg
	投与経路	Intraperitoneally

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT06065670	Not yet recruiting	Demyelinating Diseases\|Demyelination; Corpus Callosum\|Multiple Sclerosis Brain Lesion\|Multiple Sclerosis Acute and Progressive\|Clinically Isolated Syndrome CNS Demyelinating	University of California San Francisco	March 1 2024	Phase 1\|Phase 2
NCT05359653	Recruiting	Multiple Sclerosis (MS)\|Multiple Sclerosis Relapsing-Remitting\|Multiple Sclerosis Primary Progressive\|Multiple Sclerosis Chronic Progressive\|Multiple Sclerosis Relapse\|Multiple Sclerosis Brain Lesion\|Multiple Sclerosis Benign	University of California San Francisco\|United States Department of Defense	August 1 2023	Phase 1\|Phase 2
NCT05131828	Recruiting	Multiple Sclerosis	Cambridge University Hospitals NHS Foundation Trust\|University of Cambridge	March 8 2022	Phase 2
NCT02040298	Completed	Multiple Sclerosis Relapsing-Remitting	University of California San Francisco	January 2014	Phase 2
NCT01239719	Unknown status	Allergy\|Dermatitis	Azidus Brasil	March 2011	Phase 3

参考
[1] Seifert R, et al. Mol Pharmacol, 1992, 42(2), 227-234. [2] Nair MP, et al. Cell Immunol, 1983, 81(1), 45-60. [3] Merlos M, et al. J Pharmacol Exp Ther, 1997, 280(1), 114-121. [4] Ridley JM, et al. J Mol Cell Cardiol, 2006, 40(1), 107-118. [5] N?renberg W, et al. J Biol Chem, 2011, 286(13), 11067-11081. [6] Blazs G, et al. Pharmacol Res, 1997, 35(1), 65-71. [7] Li Z, et al. Research Square, 29 Jun 2020. [8] Wang X, et al. Bioengineered. 2022 Mar;13(3):7134-7146. + 展開

参考

+ 展開

化学情報

分子量	459.96	化学式	C₂₁H₂₆ClNO.C₄H₄O₄
CAS No.	14976-57-9	SDF	Download Clemastine fumarate SDFをダウンロードする
Smiles	CC(C1=CC=CC=C1)(C2=CC=C(C=C2)Cl)OCCC3CCCN3C.C(=CC(=O)O)C(=O)O
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 30 mg/mL ( (65.22 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。)

Water : Insoluble

Ethanol : 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
=	×	×

希釈計算器分子量計算器

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）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

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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