Dactolisib (BEZ235)

製品コードS1009 バッチS100915

印刷

化学情報

Chemical Structure Synonyms NVP-BEZ235 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C30H23N5O
分子量 469.55 CAS No. 915019-65-7
Solubility (25°C)* 体外 4-Methylpyridine (warmed with 50ºC water bath) 3 mg/mL (6.38 mM)
DMSO 1 mg/mL (2.12 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.
in vitro Dactolisib (BEZ235) significantly reduces the phosphorylation levels of the mTOR activated kinase p70S6K. It results in a reduction of S235/S236P-RPS6 levels with IC50 of 6.5 nM. The activity of this compound against mTOR is determined using a biochemical mTOR K-LISA assay with IC50 of 20.7 nM. It shows slightly lower activity against its β paralogue with IC50 of 75 nM. The PI3K/Akt/mTOR pathway is often constitutively activated in human tumor cells. BEZ235 blocks PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. Both PTEN-null cell lines PC3M and U87MG show a dose-dependent reduction in cell proliferation when treated with increasing concentrations of it with an average GI50 of 10-12 nM. [1] It is an mTORC1/2 catalytic inhibitor. [2]
in vivo Dactolisib (BEZ235) induces regression of the tumors (69%) without statistically significant effect on body weight gain. Altogether, these preliminary in vivo efficacy results show that this compound causes disease stasis when administered orally as a single agent and can enhance the efficacy of other anticancer agents when used in combination studies. [1]

プロトコル(参考用のみ)

キナーゼアッセイ In vitro Protein Kinase, PI3K, and mTOR Assays
PI3Kα, β, and δ proteins are composed of the iSH2 domain of p85 NH2-terminally fused to the full-length protein p110 protein, with the exception of α that also does not contain the last 20 amino acids. PI3Kγ is produced as full-length protein deleted for its first 144 amino acids. All constructs are fused to a COOH-terminal His tag for convenient purification and then cloned into the pBlue-Bac4.5 (for α, β, and δ isoforms) or pVL1393 (for γ isoform) plasmids. The different vectors are then cotransfected with BaculoGold WT genomic DNA using methods recommended by the vendor for production of the respective recombinant baculoviruses and proteins. Dactolisib (BEZ235) is tested for its activity against PI3K using a Kinase-Glo assay. The kinase reaction is done in 384-well black plate. Each well is loaded with 50 μL of test items (in 90% DMSO) and 5 μL reaction buffer containing 10 μg/mL PI substrate (l-α-phosphatidylinositol; Avanti Polar Lipids; prepared in 3% octyl-glucoside) and the PI3K proteins (10, 25, 10, and 150 nM of p110α, p110β, p110δ, and p110γ, respectively) are then added to it. The reaction is started by the addition of 5 μL of 1 μM ATP prepared in the reaction buffer and is incubated for either 60 (for p110α, p110β, and p110δ) or 120 min (for p110γ). It is terminated by the addition of 10 μL Kinase-Glo buffer. The plates are then read in a Synergy 2 reader for luminescence detection.
細胞アッセイ 細胞株 HCT116, DLD-1 and SW480 cells
濃度 0-1 μM
反応時間 48 hours
実験の流れ

The human CRC cell lines, HCT116 (PIK3CA mutant; kinase domain at H1047R), DLD-1 (PIK3CA mutant; helical domain at E545K), and SW480 (PIK3CA wild-type) and isogenic DLD-1 PIK3CA mutant as well as wild-type cells are maintained in DMEM with 10% FBS and 1 × Penicillin/Streptomycin. Cells are plated at different initial densities (HCT116: 3 × 103 cells/well, DLD-1: 5.5 × 103 cells/well, SW480: 4.5 × 103 cells/well, DLD-1 PIK3CA mutant: 7 × 103 cells/well, and DLD-1 PIK3CA wild-type: 9 × 103 cells/well) to account for differential growth kinetics. After 16 hours, cells are incubated with increasing concentrations of Dactolisib (BEZ235), and the drug-containing growth medium is changed every 24 hours. Cell viability is assessed 16 hours after the initial plating and 48 hours after initiation of treatment with this compound using the colorimetric MTS assay CellTiter 96® AQueous One Solution Cell Proliferation Assay, as per the manufacturer's instructions. Cell viability after drug treatment is normalized to that of untreated cells also grown for 48 hours. For western blot analysis, cells are plated with zero or maximum inhibitory dose (500 nM) of it for 2, 6, 24, or 48 hours.
動物実験 動物モデル Female Harlan athymic nude mice
投薬量 45 mg/kg
投与方法 p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/18606717/
  • https://pubmed.ncbi.nlm.nih.gov/21966435/
  • https://pubmed.ncbi.nlm.nih.gov/21791089/
  • https://pubmed.ncbi.nlm.nih.gov/20606035/
  • https://pubmed.ncbi.nlm.nih.gov/21412767/
  • https://pubmed.ncbi.nlm.nih.gov/22662154/
  • https://pubmed.ncbi.nlm.nih.gov/20876803/
  • https://pubmed.ncbi.nlm.nih.gov/21552262/

カスタマーフィードバック

Data from [Breast Cancer Res, 2011, 13, R52]

Data from [Breast Cancer Res, 2011, 13:R52]

Data from [Clin Cancer Res, 2010, 16, 6029-6039]

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Depleting the action of EZH2 through PI3K-mTOR inhibition to overcome metastasis and immunotherapy resistance in triple-negative breast cancer [ Mol Cancer Ther, 2025, 10.1158/1535-7163.MCT-24-0693] PubMed: 40497697
Changes in Melanoma Cell Morphology Following Inhibition of Cell Invasion by Third-Generation mTOR Kinase Inhibitors [ Int J Mol Sci, 2025, 26(16)7770] PubMed: 40869090
Extracellular Fibronectin and Hyaluronic Acid Effects on Tumorigenic Functions of Triple-Negative Breast Cancer Cells [ J Biomed Mater Res A, 2025, 113(4):e37906] PubMed: 40192931
Extracellular Fibronectin and Hyaluronic Acid Effects on Tumorigenic Functions of Triple-Negative Breast Cancer Cells [ J Biomed Mater Res A, 2025, 113(4):e37906] PubMed: 40192931
Nanoemulsification of PTX and BEZ235 inhibits colon cancer growth [ Sci Rep, 2025, 15(1):16217] PubMed: 40346124

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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