PI-103

製品コードS1038 バッチS103802

印刷

化学情報

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

C19H16N4O3
分子量 348.36 CAS No. 371935-74-9
Solubility (25°C)* 体外 DMSO 24 mg/mL (68.89 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 PI-103 is a multi-targeted PI3K inhibitor for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM in cell-free assays, less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM. PI-103 induces apoptosis in murine T-cell Lymphoma.
in vitro PI-103 potently inhibits both the rapamycin-sensitive (mTORC1) and rapamycin-insensitive (mTORC2) complexes of the protein kinase mTOR. [1] PI-103 inhibits constitutive and growth factor-induced PI3K/Akt, as well as mTORC1 activation. [2] In blast cells, PI-103 inhibits leukemic proliferation, the clonogenicity of leukemic progenitors and induces mitochondrial apoptosis, especially in the compartment containing leukemic stem cells. PI-103 inhibits p110α >200-fold more potently than p110β. PI-103 also potently blocks production of PI(3,4)P2 and PIP3 in adipocytes and PIP3 in myotubes. [2] PI-103 inhibits phosphorylation of Akt with an IC95 100-fold lower than that for LY294002. Strikingly, PI-103 completely protects animals from insulin-stimulated decline in blood glucose. PI-103 has additive proapoptotic effects with etoposide in blast cells and in immature leukemic cells. [2]
in vivo When tumors reach 50-100 mm3, animals are randomized and treated with vehicle or PI-103. PI-103 exhibits significant activity, decreasing average tumor size by 4-fold after 18 days. [2] Mice treated with PI-103 have no obvious signs of toxicity premorbidly (based on body weight, food and water intake, activity, and general exam) or at necropsy. Treated tumors display decreased levels of phosphorylated Akt and S6, consistent with blockade of p110α and mTOR. PI-103 treatment is cytostatic to glioma xenografts. [2]
特徴 The first potent, synthetic mTOR inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ Enzyme Assays
Phosphatidylinositide 3-kinase inhibitory activity was determined using a scintillation proximity assay in the presence of 1 μmol/L ATP. Inhibition of mTOR protein kinase was determined using a TR-FRET-based LanthaScreen method from Invitrogen. Compounds were assayed at a maximum concentration of 10 μmol/L in the presence of 1 μmol/L ATP, and IC50 values were determined using GraphPad Prism software.
細胞アッセイ 細胞株 U87MG cells
濃度 0.5 μM
反応時間 24 hours
実験の流れ U87MG cells are treated with PI-103 for 24 hours. Cell death is quantified by colorimetric determination of LDH activity using a cytotoxicity detection kit. Percentage of cell death (mean of three 12-well plates per experimental point) is calculated [(experimental value- low control)/(high control -low control) × 100], where the low-control cells are DMSO treated and high-control cells are Triton treated (1% Triton X-100, 30 min, 37 °
動物実験 動物モデル 6- to 12-week-old Balbc nu/nu mice bearing U87MG:ΔEGFR cells
投薬量 5 mg/kg
投与方法 Administered via i.p.

カスタマーフィードバック

, Saraswati Sukumar of Johns Hopkins University School of Medicine

Data from [Mol Carcinog, 2012, 52, 667-75 ]

Data from [Mol Carcinog, 2012, ahead of print]

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：

Young and undamaged recombinant albumin alleviates T2DM by improving hepatic glycolysis through EGFR and protecting islet β cells in mice [ J Transl Med, 2023, 21(1):89] PubMed: 36747238
RIDR-PI-103, ROS-activated prodrug PI3K inhibitor inhibits cell growth and impairs the PI3K/Akt pathway in BRAF and MEK inhibitor-resistant BRAF-mutant melanoma cells [ Anticancer Drugs, 2023, 34(4):519-531] PubMed: 36847042
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies [ Blood, 2022, blood.2021014304] PubMed: 35704690
Systematic identification of biomarker-driven drug combinations to overcome resistance [ Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7] PubMed: 35332332
Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma [ Br J Cancer, 2022, 10.1038/s41416-022-01973-6] PubMed: 36097178
(+)-Cyanidan-3-ol inhibits epidermoid squamous cell carcinoma growth via inhibiting AKT/mTOR signaling through modulating CIP2A-PP2A axis [ Phytomedicine, 2022, 101:154116] PubMed: 35525235
In Vitro Angiogenesis Inhibition and Endothelial Cell Growth and Morphology [ Int J Mol Sci, 2022, 23(8)4277] PubMed: 35457095
PD-L1 deficiency sensitizes tumor cells to DNA-PK inhibition and enhances cGAS-STING activation [ Am J Cancer Res, 2022, 12(5):2363-2375] PubMed: 35693073
Enhanced Vulnerability of LKB1-Deficient NSCLC to Disruption of ATP Pools and Redox Homeostasis by 8-Cl-Ado [ Mol Cancer Res, 2022, 20(2):280-292] PubMed: 34654720

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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