Cilomilast

製品コードS1455 バッチS145501

化学情報

	Synonyms	SB-207499	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₀H₂₅NO₄
	分子量	343.42	CAS No.	153259-65-5
Solubility (25°C)*	体外	DMSO	69 mg/mL (200.92 mM)
		Ethanol	50 mg/mL (145.59 mM)
		Water	Insoluble
* <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	Cilomilast (SB-207499) is a potent PDE4 inhibitor with IC50 of about 110 nM, has anti-inflammatory activity and low central nervous system activity. Phase 3.
in vitro	Cilomilast produces a concentration-dependent increase in cAMP content in U937 cells. Cilomilast produces a concentration-dependent increase in cAMP content in U937 cells. ^[2] In isolated human monocytes, Cilomilast and (R)-rolipram are equipotent at suppressing LPS-induced TNF-α formation with -log (IC50) of 7.0 and 7.2, respectively. Both Cilomilast and (R)-rolipram produces a modest prevention of fMLP-induced degranulation of human neutrophils. Cilomilast and (R)-rolipram are equipotent at suppressing neutrophil activation with -log (IC50) of 7.1 and 6.4, respectively. ^[2] Cilomilast significantly decreases the expression of TNF-α in the cornea and IL-1α, IL-1β, and TNF-α in the conjunctivaas compared to vehicle control. Cilomilast treatment markedly decreases the presence of CD11b+ antigen-presenting cells in the central and peripheral cornea, and leads to decreased conjunctival expression of cytokines IL-6, IL-23, and IL-17. Moreover, Cilomilast decreases the expression of IL-17 and IL-23 in the draining lymph nodes. ^[3] Cilomilast reduces TLR4 expression, IL-8 release and neutrophil chemotactic activity as well as it increased IP-10 release and lymphocyte chemotactic activity. ^[4]
in vivo	Cilomilast inhibits human TNFα production with oral ED50 of 4.9 mg/kg. In contrast to their equipotent activity against TNFα production, Cilomilast (ED50 = 2.3 mg/kg, p.o.) is 10-fold less potent than R-rolipram (ED50 = 0.23 mg/kg, p.o.) in reversing reserpine-induced hypothermia, a model of antidepressant activity. ^[1] In time course studies, Cilomilast (30 mg/kg, p.o.) suppresses TNFα production for at least 10 hour. The ability of Cilomilast to modulate interleukin-4 productionin vivo is assessed in a chronic oxazolone-induced contact sensitivity model in Balb/c mice. Topical administration of Cilomilast (1000 μg) inhibits intralesional concentrations of interleukin-4. ^[1] Orally administered cilomilast dose-dependently inhibits production of interleukin-4, TNF-α, and cysteinyl leukotrienes, as well as leukocyte infiltration in bronchoalveolar lavage fluid from the airways of ovalbumin-sensitized Brown Norway rats ^[5].
特徴	Cilomilast has been used to treat chronic obstructive pulmonary disease (COPD) for many years.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	U937 cells
	濃度	0.1-10 μM
	反応時間	5 min
	実験の流れ	U937 cells (1-2 × 10 ⁶) are incubated at 37 °C in a shaking water bath with Cilomilast for 1 min before the addition of 0.1 μM PGE₂ (total volume of 200 μL). The incubation proceeds for an additional 4 min and is stopped by the addition of 0.1 mL of HClO₄ (17.5%), neutralized with 0.15 ml of K₂₃ (1.0 M) and diluted to 1 mL with sodium acetate buffer. Samples are centrifuged at 3000 × g for 10 min. Aliquots of the supernatant fraction are assayed for cAMP content by radioimmunoassay using commercially available kits.
動物実験	動物モデル	Balb/c, CD-1 and C57B1/6 male mice weighing from 18 to 25 g with human monocytes or endotoxin-induced shock
	投薬量	3, 6, 12, 25, 50 mg/kg
	投与方法	Gavage

参考

+ 展开

カスタマーフィードバック

: Data from [Data independently produced by Mol Cancer Res, 2014, 10.1158/1541-7786.MCR-14-0110]

: Data from [Biochimie, 2012, 94, 2360e2365 ]

: Data from [Biochimie, 2012, 94, 2360e2365 ]

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：

Inhibition of PDE4/PDE4B improves renal function and ameliorates inflammation in cisplatin-induced acute kidney injury. [ Am J Physiol Renal Physiol, 2020, 318(3):F576-F588]	PubMed: 31961716
A multi-targeted liquid chromatography–mass spectrometryscreening procedure for the detection in human urine of drugsnon-prohibited in sport commonly used by the athletes [Mazzarino M, et al. J Pharm Biomed Anal, 2016, 117:47-60]	PubMed: 26342446
Inhibitors of Phosphodiesterase 4, but Not Phosphodiesterase 3, Increase β2-Agonist–Induced Expression of Antiinflammatory Mitogen-Activated Protein Kinase Phosphatase 1 in Airway Smooth Muscle Cells [Patel BS Am J Respir Cell Mol Biol, 2015, 52(5):634-40]	PubMed: 25296132
Phosphodiesterase 4D inhibitors limit prostate cancer growth potential [ Mol Cancer Res, 2015, 13(1):149-60]	PubMed: 25149359
Phosphodiesterase 4D Inhibitors Limit Prostate Cancer Growth Potential [Powers GL, et al. Mol Cancer Res, 2015, 13(1):149-60]
Inhibitors of Phosphodiesterase 4, but Not Phosphodiesterase 3, Increase b2-Agonist–Induced Expression of Antiinflammatory Mitogen-Activated Protein Kinase Phosphatase 1 in Airway Smooth Muscle Cells [Patel BS, et al. AM J Resp Cell Mol, 2014, 10.1165/rcmb.2014-0344OC]
Monitoring phosphodiesterase‐4 inhibitors using liquid chromatography/(tandem) mass spectrometry in sports drug testing [Thevis M Rapid Commun Mass Spectrom, 2013, 27(9):993-1004]	PubMed: 23592202
Cilomilast enhances osteoblast differentiation of mesenchymal stem cells and bone formation induced by bone morphogenetic protein 2. [Munisso MC, et al. Biochimie, 2012, 94(11):2360-5]	PubMed: 22706281

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。