GSK046 (iBET-BD2)

製品コードS9684 バッチS968401

印刷

化学情報

Chemical Structure Synonyms Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C23H27FN2O4
分子量 414.47 CAS No. 2474876-09-8
Solubility (25°C)* 体外 DMSO 83 mg/mL (200.25 mM)
Ethanol 83 mg/mL (200.25 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 GSK046 (iBET-BD2) is a selective and orally active inhibitor of BET (bromodomain and extraterminal domain) with IC50 of 264 nM, 98 nM, 49 nM and 214 nM for BRD2BD2, BRD3BD2, BRD4BD2 and BRDTBD2, respectively. GSK046 exhibits immunomodulatory activity.
in vitro

GSK046 shows an excellent level of selectivity for the BET family with no measurable activity for non-BET bromodomains. GSK046 is tested in an LPS-stimulated peripheral blood mononuclear cell (PBMC) cellular assay. After stimulation, these immune cells release a range of cytokines and chemokines, including monocyte chemoattractant protein 1 (MCP-1/CCL2). GSK046 also inhibits MCP-1 production (pIC50 = 7.5) with a minimal drop-off from the biochemical BRD4 BD2 potency observed.[2]
in vivo

GSK046 has suitable physicochemical and pharmacokinetic properties to be utilized in vivo, and it has also been demonstrated that a highly selective BD2 inhibitor retains the ability to potently inhibit MCP-1 cytokine release in a cellular and whole blood context. GSK046 proves useful for further biological profiling. GSK046 is efficacious in a broad range of inflammatory pathologies and selective BD2 inhibition may be a useful new therapeutic strategy for immunoinflammatory diseases.[2]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 PBMCs, hepatocytes
濃度 0.5 μM
反応時間 5 min, 10 min, 20 min, 40 min, 60 min, 120 min
実験の流れ

The metabolic stability of GSK046 is tested in male Wistar Han rat, male Beagle dog and mixed gender pooled human hepatocytes. Suspensions of cryopreserved hepatocytes from each species are used. Incubations are performed at a test or control compound concentration of 0.5 μM at 37 °C, at a cell density of 0.5 million viable cells/mL. Control incubations are also performed in lysed cells to reveal any non-enzymatic degradation. For Rat and Human incubation samples (50 μL) are removed from the incubation mixture at 0, 5, 10, 20, 40 and 60 min. For Dog incubation samples (50 μL) are removed from the incubation mixture at 0, 10, 20, 40, 60 and 120 min. The samples are added to methanol, containing internal standard, (100 μL) to stop the reaction. Following protein precipitation, the compound remaining in the supernatants is measured using specific LC-MS/MS methods as a ratio to the internal standard in the absence of a calibration curve. Peak area ratios (Compound to IS) are fitted to an unweighted logarithmic decline in substrate. Using the first order rate constant, clearance is calculated by adjustment for protein concentration, volume of the incubation and hepatic scaling factor.
動物実験 動物モデル male Wistar Han Rats, male Beagle dogs
投薬量 0.5 mg/kg, 1 mg/kg, 3 mg/kg
投与方法 IV, Oral gavage

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。

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