Apremilast

別名：CC-10004

製品コード：S8034 純度：99.98%

Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively.

CAS No. 608141-41-9

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 55500	国内在庫あり
5mg	JPY 40500	国内在庫あり
25mg	JPY 130500	国内在庫あり
1g	JPY 598500	国内在庫なし(納期7~10日)

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

文献中Selleckの製品使用例（8）

製品安全説明書

現在のバッチを見る：純度： 99.98%

99.98

Apremilast関連製品

関連ターゲット	PDE1 PDE2 PDE3 PDE4 PDE5 PDE6 PDE10A PDE9 PDE4B	もっと見る
関連化合物ライブラリー	Metabolism Compound Library Anti-cancer Metabolism Compound Library Glutamine Metabolism Compound Library Carbohydrate Metabolism Compound Library Lipid Metabolism Compound Library	もっと見る

シグナル伝達経路

PDEシグナル伝達経路

PDE阻害剤の選択性比較

生物活性

製品説明

Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively.

Targets

PDE4 ^[1]	TNF-α ^[1]
74 nM	77 nM

In Vitro
In vitro	Apremilast is more potent for inhibition of PDE4 compared with cAMP or cGMP hydrolysing enzymes from other PDE families. Apremilast displays a broad pattern of anti-inflammatory activity in a variety of cell types, inhibits TNF-α, IL-12 and IL-23 production, as well as NK and keratinocyte responses. Apremilast is found to inhibit the zymosan-induced PMN production of IL-8 with IC50 of 94 nM. Apremilast inhibits fMLF-induced PMN CD18 and CD11b expression with IC50 of 390 nM and 74 nM, respectively, and inhibits fMLF-induced adhesion of PMN to HUVECs with IC50 of 150 nM. Apremilast inhibits keratinocyte TNF-αproduction, with no effect on keratinocyte cell viability as measured by intracellular ATP levels. ^[3] ^[4].
Kinase Assay	PDE4 inhibitory activity
Kinase Assay	Cells (1×10⁹) are washed in PBS and lysed in cold homogenization buffer (20 mM Tris-HCl, pH 7.1, 3 mM 2-mercaptoethanol, 1 mM MgCl₂, 0.1 mM EGTA, 1 μM PMSF, 1 μg/mL leupeptin). Following homogenization in a Dounce homogenizer the supematant is collected by centrifugation and loaded onto a Sephacryl S-200 column equilibrated in homogenization buffer. PDE is eluted in homogenization buffer and the rolipram sensitive fractions pooled and stored in aliquots. Enzyme activity is assayed in 50 mM Tris- HCl, pH 7.5, 5 mM MgCl₂ and 1 μM cAMP (of which 1% is³H cAMP) in the presence of varying concentrations of inhibitors. The amount of extract used is pre-determined to ensure that reactions are within the linear range and consumed lessthan15%of the total substrate. Reactions are performed at 30°C for 30 min and terminated by boiling for 2 min. The samples are then chilled and treated with snake 'venom (1mg/mL) at 30 °C for 15 min. Unused substrate is removed by incubation with 200 μL AG1-X8 resin for 15 min. Samples are then spun at 3000 rpm for 5 min and 50 μL of the aqueous phase taken for counting. Eachdata point is carried out in duplicate with activity expressed as percentage of control. IC50 is determined from dose response curves derived from three independent experiments.
細胞実験	細胞株	HEKn cells
	濃度	~10 μM
	反応時間	18 h
	実験の流れ	For proliferation studies, human neonatal foreskin epidermal keratinocytes (HEKn cells) are plated at 3000 cells per well in 96-well flat bottom tissue culture plates for 2 days. HEKn cells are treated with apremilast or 0.1% DMSO as the vehicle control for 1 h before ultraviolet B (UVB) irradiation with 50 mJ/cm² in a UV Stratalinker 2400, calibrated with 312 nm UVB bulbs. Media and compounds are replaced, and cells are incubated for 18 h. Lysates are transferred to plates and shaken for 2 min before chemiluminescence is read on a TopCount NXT Luminescence Counter.

In Vivo
In Vivo	Apremilast is stable in the presence of human microsomes (t1/2 > 60 min). It is 90% protein bound in human plasma. Oral and intravenous administration of it in female rats showed that it have good pharmacokinetics with low clearance, a moderate volume of distribution, and a 64% oral bioavailability. In a LPS-induced TNF-αinhibition model in rats, examined the TNF-α inhibitory ability of Apremilast in vivo, and the ED50 is determined to be 0.03 mg/kg. In another LPS-induced neutrophilia model in rats, Apremilast exhibited an ED50 range from 0.3 mg/kg to 0.9 mg/kg.^[1]
動物実験	動物モデル	Psoriasis mouse model
	投与量	5 mg/kg/day, divided into b.i.d.doses
	投与経路	Oral

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT06122649	Recruiting	Plaque Psoriasis	Amgen	November 27 2023	Phase 3
NCT06108544	Recruiting	Plaque Psoriasis	Takeda	November 6 2023	Phase 3
NCT06088043	Recruiting	Plaque Psoriasis	Takeda	November 6 2023	Phase 3
NCT05926882	Completed	Alopecia Areata	Jinnah Postgraduate Medical Centre	August 1 2022	Phase 4
NCT04804553	Recruiting	Active Juvenile Psoriatic Arthritis	Amgen	March 17 2022	Phase 3
NCT04528082	Recruiting	Behçet Disease	Amgen	September 9 2021	Phase 3

参考
[1] Man HW, et al. J Med Chem, 2009,52(6), 1522-1524. [2] Muller GW, et al. Bioorg Med Chem Lett, 1998,8(19), 2669-2674. [3] PH Schafer, et al. Br J Pharmacol, 2010, 159(4), 842–855. [4] Fiona E McCann,et al. Arthritis Res Ther, 2010, 12(3), R107. + 展開

参考

[4] Fiona E McCann,et al. Arthritis Res Ther, 2010, 12(3), R107.

+ 展開

化学情報

分子量	460.5	化学式	C₂₂H₂₄N₂O₇S
CAS No.	608141-41-9	SDF	--
Smiles	CCOC1=C(C=CC(=C1)C(CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC
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个月-20°Cin solvent

In vitro
Batch:

DMSO : 92 mg/mL ( (199.78 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。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):