Aclidinium Bromide

別名：LAS 34273, LAS-W 330

製品コード：S4031 純度：99.56%

Aclidinium Bromide (LAS 34273, LAS-W 330) inhibits human muscarinic AChR M1, M2, M3, M4 and M5 with K_i of 0.1 nM, 0.14 nM, 0.14 nM, 0.21 nM and 0.16 nM, respectively.

CAS No. 320345-99-1

サイズ	価格(税別)	在庫状況
10mg	JPY 25500	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

製品安全説明書

現在のバッチを見る： S403102 DMSO] 71 mg/mL] false] Water] Insoluble] false] Ethanol] Insoluble] false 純度： 99.56%

99.56

Aclidinium Bromide関連製品

関連ターゲット	mAChR nAChR AChE	もっと見る
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関連化合物ライブラリー	FDA-approved Drug Library Natural Product Library Neuronal Signaling Compound Library CNS-Penetrant Compound Library Anti-alzheimer Disease Compound Library	もっと見る

シグナル伝達経路

AChRシグナル伝達経路

AChR阻害剤の選択性比較

生物活性

製品説明

Aclidinium Bromide (LAS 34273, LAS-W 330) inhibits human muscarinic AChR M1, M2, M3, M4 and M5 with K_i of 0.1 nM, 0.14 nM, 0.14 nM, 0.21 nM and 0.16 nM, respectively.

特性

Approximately equipotent to Tiotropium, and 8-16 times more potent than Ipratropium for muscarinic receptor subtypes.

Targets

M1 mAChR ^[1]	M2 mAChR ^[1]	M3 mAChR ^[1]	M5 mAChR ^[1]	M4 mAChR ^[1]
0.1 nM(Ki)	0.14 nM(Ki)	0.14 nM(Ki)	0.16 nM(Ki)	0.21 nM(Ki)

In Vitro
In vitro	[³H]Aclidinium binds to a homogeneous receptor of M2 with Kd of 0.34 nM and Bmax of 3.13 pmol/mg, and binds to M3 with Kd of 0.34 nM and Bmax of 3.13 pmol/mg. Aclidinium (< 100 nM) dose-dependently inhibits carbachol-induced contractions in isolated guinea pig trachea. Aclidinium shows an onset of action with t_1/2 of 6.8 min, t_max of 35.9 min in isolated guinea pig trachea. ^[1] Aclidinium is hydrolysed in plasma samples from all species studied, with apparent half-lives at 37℃ of 11.7 min, 38.3 min, 1.8 min and 2.4 min in rat, guinea pig, dog and human plasma, respectively. ^[2] Aclidinium (0.1 μM) inhibits carbachol and TGF-β1 induced upregulation of collagen type I and α-SMA mRNA and protein expression in human bronchial fibroblasts. Aclidinium (0.1 μM) inhibits TGF-β1 induced upregulation of ChAT expression in human bronchial fibroblasts. Aclidinium (0.1 μM) inhibits carbachol- and TGF-β1-induced increases in ERK1/2 phosphorylation and RhoA-GTP formation in human bronchial fibroblasts. Aclidinium pretreatment prevents the upregulation of M1 and M3, but not M2 downregulation induced by carbachol or TGF-β1 in human lung fibroblasts. Aclidinium (0.1 μM) dose-dependently inhibits the TGF-β1 and carbachol-induced cell proliferation of human lung fibroblasts. ^[3]
Kinase Assay	Affinity assay
Kinase Assay	The affinity of Aclidinium for the different human muscarinic receptor subtypes at equilibrium is determined by measuring their ability to displace the binding of [³H]NMS to cell membrane preparations expressing one of the human muscarinic receptor subtypes. Protein concentrations are 8.1 μg/well, 10.0 μg/well, 4.9 μg/well, 4.5 μg/well, and 5.0 μg/well for M1, M2, M3, M4, and M5 receptor membrane preparations, respectively. The assays are conducted at [³H]NMS concentrations approximately equal to the radioligand equilibrium dissociation constant (Kd) for the different muscarinic receptors subtypes. The [³H]NMS concentration is 0.3 nM for the M1 and M4 assays and 1 nM for the M2, M3, and M5 assays. A range of antagonist concentrations (10⁻¹⁴ to 10⁻⁵ M) are tested in duplicate to generate competition curves. Nonspecific binding is determined in the presence of atropine (1 μM). Assay reagents are dissolved in assay binding buffer (phosphate-buffered saline with calcium and magnesium) to a total volume of 200 μL. After a 2 hours or 6 hours incubation period (M1–M4 and M5, respectively) at room temperature in 96-well microtiter plates to ensure that equilibrium is achieved for Aclidinium, 150 μL aliquots of the reaction are transferred to GF/C filter plates pretreated for 1 hour with wash buffer (50 mM Tris, 100 mM NaCl, pH 7.4) containing 0.05% polyethylenimine. Bound and free [³H]NMS are then separated by rapid vacuum filtration followed by four washes with ice-cold wash buffer. Filters are then dried for 30 min before addition of 30 μL of OptiPhase Supermix, and radioactivity is quantified using a MicroBeta Trilux microplate scintillation counter.
細胞実験	細胞株	Human bronchial fibroblast
	濃度	100 nM
	反応時間	48 hours
	実験の流れ	Human bronchial fibroblast proliferation is measured as previously outlined by colorimetric immunoassay based on BrdU incorporation during DNA synthesis using a cell proliferation enzyme-linked immunosorbent assay BrdU kit according to the manufacturer’s protocol. Cells are seeded at a density of 3x10³ cells/well on 96-well plates and incubated for 24 hours. Cells are then exposed to different experimental conditions. The 490 nm absorbance is quantified using a microplate spectrophotometer. Proliferation data refers to the absorbance values of BrdU-labeled cellular DNA content per well. Stimulation is expressed as x-fold proliferation over basal growth of the untreated control set as unity.

In Vivo
In Vivo	Aclidinium shows an onset of action with IC50 (95% CI) of 140 μg/mL and t_max of 30 min in the acetylcholine-induced bronchoconstriction model in anesthetized guinea pigs. Aclidinium (500 μg/kg) induces a maximal increase in heart rate of 55% after 1 hour in conscious beagle dogs. ^[1] Aclidinium (1 mg/ml) produces a potent and sustained bronchoprotection (72%–88.4%) over the 120-min study period in anaesthetised guinea pigs. ^[2]
動物実験	動物モデル	beagle dogs
	投与量	500 μg/kg
	投与経路	Administered by using a nebulizer

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT03276078	Completed	Pulmonary Disease Chronic Obstructive	AstraZeneca	November 23 2017	Phase 2

参考
[1] Gavald?A, et al. J Pharmacol Exp Ther, 2009, 331(2), 740-751. [2] Sentellas S, et al. Eur J Pharm Sci, 2010, 39(5), 283-290. [3] Milara J, et al. Thorax, 2012, 67(3), 229-237.

参考

化学情報

分子量	564.55	化学式	C₂₆H₃₀NO₄S₂.Br
CAS No.	320345-99-1	SDF	--
Smiles	C1C[N+]2(CCC1C(C2)OC(=O)C(C3=CC=CS3)(C4=CC=CS4)O)CCCOC5=CC=CC=C5.[Br-]
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 : 71 mg/mL ( (125.76 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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