Taselisib (GDC 0032)

製品コードS7103 バッチS710301

印刷

化学情報

Chemical Structure Synonyms RG7604 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H28N8O2
分子量 460.53 CAS No. 1282512-48-4
Solubility (25°C)* 体外 DMSO 70 mg/mL warmed with 50ºC water bath (151.99 mM)
Ethanol 7 mg/mL warmed with 50ºC water bath (15.19 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 Taselisib (GDC 0032, RG7604) is a potent, next-generation β isoform-sparing PI3K inhibitor targeting PI3Kα/δ/γ with Ki of 0.29 nM/0.12 nM/0.97nM, >10 fold selective over PI3Kβ.
in vitro GDC-0032 is an orally bioavailable, potent, and selective inhibitor of Class I PI3Kα, δ, and γ isoforms, with 30 fold less inhibition of the PI3K β isoform relative to the PI3Kα isoform. Preclinical data show that GDC-0032 has increased activity against PI3Kα isoform (PIK3CA) mutant and HER2-amplified cancer cell lines. GDC-0032 inhibits MCF7-neo/HER2 cells proliferation with IC50 of 2.5 nM. [1]
in vivo GDC-0032 pharmacokinetics is approximately dose proportional and time independent with a mean t1/2 of 40 hours. The combination of GDC-0032 enhances activity of fulvestrant resulting in tumor regressions and tumor growth delay (91% tumor growth inhibition (TGI)). In addition, the combination of GDC-0032 with tamoxifen enhances the efficacy of tamoxifen in vivo (102%TGI for GDC-0032). [1]
特徴 A beta isoform-sparing PI3K inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ Characterization of Biochemical and Cellular Activity in Vitro
Enzymatic activity of the class I PI3K isoforms is measured using a fluorescence polarization assay that monitors formation of the product 3,4,5-inositoltriphosphate molecule as it competes with fluorescently labeled PIP3 for binding to the GRP-1 pleckstrin homology domain protein. An increase in phosphatidyl inositide-3-phosphate product results in a decrease in fluorescence polarization signal as the labeled fluorophore is displaced from the GRP-1 protein binding site. Class I PI3K isoforms are expressed and purified as heterodimeric recombinant proteins. Tetramethylrhodamine-labeled PIP3 (TAMRA-PIP3), di-C8-PIP2, and PIP3 detection reagents are purchased from Echelon Biosciences. PI3Kα is assayed under initial rate conditions in the presence of 10 mM Tris (pH 7.5), 25 μM ATP, 9.75 μM PIP2, 5% glycerol, 4 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, and 2% (v/v) DMSO at 60 ng/mL. After assay for 30 min at 25 °C, reactions are terminated with a final concentration of 9 mM EDTA, 4.5 nM TAMRA-PIP3, and 4.2 μg/mL GRP-1 detector protein before reading fluorescence polarization on an Envision plate reader. IC50 values are calculated from the fit of the dose-response curves to a 4-parameter equation. Each reported value is an average of three experiments, and all have a standard deviation less than one geometric mean.
細胞アッセイ 細胞株 MCF7-neo/HER2 Cells
濃度
反応時間 3 and 4 days
実験の流れ MCF7-neo/HER2 cells are seeded in 384-well plates in media at 1000 cells/well and incubated overnight prior to the addition of compounds to a final DMSO concentration of 0.5% v/v. MCF7-neo/HER2 cells are incubated for 3 and 4 days, respectively, prior to the addition of CellTiter-Glo reagent and reading of luminescence using an Analyst plate reader. For antiproliferative assays, a cytostatic agent such as aphidicolin and a cytotoxic agent such as staurosporine are included as controls.
動物実験 動物モデル MCF7-neo/Her2 xenograft model
投薬量 1.4, 2.8, 5.8, 11.25, or 22.5 mg/kg
投与方法 oral

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：

AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis [ Nat Commun, 2024, 15(1):686] PubMed: 38263319
Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer [ Eur J Pharmacol, 2023, 948:175703] PubMed: 37028543
Selective Inhibition of PI3K Isoforms in Brain Tumors Suppresses Tumor Growth by Increasing Radiosensitivity [ Yonsei Med J, 2023, 64(2):139-147] PubMed: 36719022
PI3K drives the de novo synthesis of coenzyme A from vitamin B5 [ Nature, 2022, 608(7921):192-198] PubMed: 35896750
MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [ Cancer Cell, 2022, S1535-6108(21)00662-0] PubMed: 35051357
The Oncogenic PI3K-Induced Transcriptomic Landscape Reveals Key Functions in Splicing and Gene Expression Regulation [ Cancer Res, 2022, 82(12):2269-2280] PubMed: 35442400
Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies [ NPJ Precis Oncol, 2022, 6(1):75] PubMed: 36274097
Dual inhibition of the MEK/ERK and PI3K/AKT pathways prevents pulmonary GVHD suppressing perivenulitis and bronchiolitis [ Blood Adv, 2022, bloodadvances.2021006678] PubMed: 35468620
PTRF/Cavin-1 as a Novel RNA-Binding Protein Expedites the NF-κB/PD-L1 Axis by Stabilizing lncRNA NEAT1, Contributing to Tumorigenesis and Immune Evasion in Glioblastoma [ Mol Oncol, 2022, 16(5):1091-1118] PubMed: 34748271
Dual Inhibition of Myc Transcription and PI3K Activity Effectively Targets Colorectal Cancer Stem Cells [ Cancers (Basel), 2022, 14(3)673] PubMed: 35158939

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。