Paxalisib (GDC-0084)

製品コードS8163 バッチS816306

印刷

化学情報

Chemical Structure Synonyms RG7666 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H22N8O2
分子量 382.42 CAS No. 1382979-44-3
Solubility (25°C)* 体外 DMSO 10 mg/mL (26.14 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 Paxalisib (GDC-0084, RG7666) is a brain penetrant inhibitor of PI3K and mTOR.
in vitro GDC-0084 has excellent human metabolic stability in microsomal and hepatocyte incubations and demonstrated inhibition of pAKT, a key signal within the PI3K pathway, in normal brain tissue[1]. GDC-0084 is shown to inhibit the proliferation of several glioma cells in vitro with IC50 ranging from 0.3 to 1.1 μM. GDC-0084 binding to plasma proteins is low, with a free fraction (%) of 29.5±2.7 (n=3) in CD-1 mouse plasma, when tested at 5 μM. Binding to brain tissues from CD-1 mice is higher, with a free fraction of 6.7% (±1; n=3)[2].
in vivo GDC-0084 markedly inhibits the PI3K pathway in mouse brain, causing up to 90% suppression of the pAkt signal. GDC-0084 achieves significant tumor growth inhibition of 70% and 40% against the U87 and GS2 orthotopic models, respectively. GDC-0084 distribution throughout the brain and intracranial tumors leads to potent inhibition of the PI3K pathway. It is being evaluated in patients, and exposures reached at tolerated doses are consistent with those associated with efficacious doses in mouse models[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Madin-Darby canine kidney (MDCK) cells （MDR1-MDCKI cells）
濃度 5 μM
反応時間 2 h
実験の流れ For transport studies, cells are seeded on 24-well Millicell plates 4 days prior to use(polyethylene terephtalate membrane, 1 μm pore size) at a seeding density of 1.3×105 cells/ml). GDC-0084 is tested at 5 μM in the apical-tobasolateral (A-B) and basolateral-to-apical (B-A) directions. The compound is dissolved in transport buffer consisting of Hanks' balanced salt solution with 10 mM HEPES. Lucifer Yellow is used as the paracellular and monolayer integrity marker. GDC-0084 concentrations in the donor and receiving compartments are determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The apparent permeability (Papp), in the apical to A-B and B-A directions, is calculated after 2-hour incubation.
動物実験 動物モデル Male Sprague−Dawley rats or female CD-1 mice
投薬量 1 mg/kg（i.v.）;5 or 25 mg/kg(p.o.)
投与方法 i.v. or p.o.

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：

Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth [ Cell Death Discov, 2023, 9(1):172] PubMed: 37202382
Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth [ Cell Death Discov, 2023, 9(1):172] PubMed: 37202382
Liver Endothelium Promotes HER3-Mediated Cell Survival in Colorectal Cancer with Wild-Type and Mutant KRAS [ Mol Cancer Res, 2022, 20(6):996-1008] PubMed: 35276002
Humanized Stem Cell Models of Pediatric Medulloblastoma Reveal an Oct4/mTOR Axis that Promotes Malignancy. [ Cell Stem Cell, 2019, 10.1016/j.stem.2019.10.005] PubMed: 31786016

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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