Bisindolylmaleimide IX (Ro 31-8220) Mesylate

製品コードS7207 バッチS720702

化学情報

	Synonyms		Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₅H₂₃N₅O₂S.CH₄O₃S
	分子量	553.65	CAS No.	138489-18-6
Solubility (25°C)*	体外	DMSO	100 mg/mL (180.61 mM)
		Water	Insoluble
		Ethanol	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	Bisindolylmaleimide IX (Ro 31-8220 Mesylate) is a pan-PKC inhibitor with IC50 of 5 nM, 24 nM, 14 nM, 27 nM, and 24 nM for PKC-α, PKC-βI, PKC-βII, PKC-γ, and PKC-ε, respectively, and also shows potent inhibition against MAPKAP-K1b, MSK1, GSK3β and S6K1.
in vitro	Ro 31-8220 inhibits rat brain PKC activity with IC50 of 23 nM, and does not show any high degree of selectivity between PKC-α, PKC-β, PKC-γ, and PKC-ε. ^[1] Ro 31-8220 also inhibits MSK1, MAPKAPK1, RSK, GSK3β and S6K1 with a potency similar to that for PKC. In addition, Ro 31-8220 inhibits voltage-dependent Na+ channels. ^[2] Ro 31-8220 alters cellular protein kinase C localization and potently inhibits growth of A549 and MCF-7 cells with IC50 of 0.78 μM and 0.897 μM, respectively. ^[3] RO 31-8220 enhances epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation. ^[4] Ro 31-8220 significantly decreases apoE secretion from primary human macrophages by inhibiting vesicular transport of apoE to the plasma membrane without significantly affecting apoE mRNA or apoE protein levels. ^[5]
in vivo	In MLP−/− Mice, Ro 31-8220 (6 mg/kg/d, s.c.) results in a significant increase in cardiac contractility. ^[6]

プロトコル(参考用のみ)

キナーゼアッセイ	Assay of PKC Activity
キナーゼアッセイ	Assay mixtures contain 0.2 mg/mL peptide-gamma, 10 μM MgCl₂, 0.6 mM CaCl₂, 10 μM [γ-³²P]ATP, 1.25 mg/mL phosphatidylserine and 1.25 ng/mL phorbol 12-myristate 13-acetate in 20 mM Hepes (pH 7.5), 2 mM EDTA, 1 mM dithiothreitol and 0.02% (w/v) Triton X-100. Peptide-γ is a synthetic peptide, GPRPLFCRKGSLRQKW, resembling the PKC-γ pseudosubstrate site, except that a serine residue replaces the pseudosubstrate alanine, converting the peptide from an inhibitor into a substrat. The assays are started by the addition of 2.5 m-units of enzyme, incubated at 30 °C for 10 min and terminated by spotting on to P81 paper, followed by extensive washing in 75 mM orthophosphoric acid. The papers are then washed in ethanol, dried, and incorporated radioactivity is determined by liquidscintillation spectroscopy.
細胞アッセイ	細胞株	Human A549 lung and MCF-7 breast carcinoma cells
	濃度	2.5 μM
	反応時間	24-48 hours
	実験の流れ	Human A549 lung and MCF-7 breast carcinoma cells are obtained from the European Collection of Animal Cell Cultures. Cells (passage number 10-30) are cultured in an atmosphere of 5% carbon dioxide, the former in Ham's F-12 medium with penicillin/streptomycin, the latter in minimum essential medium (Eagle's modification) with additional pyruvate (1 mM) and non-essential amino acids. Both media are supplemented with 10% FCS and glutamine (2 mM). Cells are subcultured routinely twice weekly to maintain logarithmic growth. For cell proliferation studies cells are seeded and incubated with 3 ml of medium including agents, which is replenished at intervals of 48 h (A549) or 72 h (MCF-7). Following incubation for 4 days (A549) or 6 days (MCF-7) with drugs, cell number is assessed using a Coulter Counter Model ZM. In order to achieve PKC depletion, cells are incubated for 24 h with bryostatin 1 (1 μM). Under these conditions growth inhibition caused by bryostatin 1 is negligible. Bryostatin is removed by extensive washing of the cells followed by a 2 h recovery period. In previous work using the A549 cell line this washing procedure has been shown to eliminate bryostatin-mediated effects. The cells are then incubated for a further 24 h with staurosporine, RO 31-8220, UCN-01 or H-7. In some experiments cells are incubated with inhibitor for 48 rather than 24 h, in this case bryostation was not removed and left in the incubate. After removal of agents inhibition of DNA synthesis is evaluated by measurement of [³H]Tdr incorporation into cell. Radioactivity is counted using a Packard 1500 Tricarb scintillation counter.
動物実験	動物モデル	MLP^−/− Mice
	投薬量	6 mg/kg/d
	投与方法	s.c.

参考

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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。

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