Buparlisib (BKM120)

製品コードS2247 バッチS224705

印刷

化学情報

Chemical Structure Synonyms NVP-BKM120 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H21F3N6O2
分子量 410.39 CAS No. 944396-07-0
Solubility (25°C)* 体外 DMSO 82 mg/mL (199.8 mM)
Ethanol 82 mg/mL (199.8 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 Buparlisib (BKM120, NVP-BKM120) is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Buparlisib induces apoptosis. Phase 2.
in vitro Buparlisib (BKM120) is not sensitive to Class III and Class IV PI3K's or PI4K. It shows great antiproliferation activity to PI3K deregulated cell lines including A2780, U87MG, MCF7 and DU145 with GI50 of 0.1-0.7 nM. [1] This compound induces multiple myeloma cells (ARP1, ARK, MM.1S, MM1.R and U266) apoptosis, which results in increased G1-phase cells and decreased S-phase cells. It induced CD138+ primary MM cell apoptosis and has significant lower cytotoxicity toward CD138− stromal cells. Its exposure could cause upregulation of BimS and downregulation of XIAP. [2] It demonstrates antiproliferative activity in human gastric cancer cell lines by decreasing mTOR downstream signaling. It could increase either p-ERK or p-STAT3 in KRAS mutant gastric cancer cells. Combination with STAT3 blockade, it shows a synergism in cells harboring mutated KRAS by inducing apoptosis, but not in KRAS wild-type cells. [3] A recent study shows that it shows differential forms of cell death on the basis of p53 status of the cells with p53 wild-type cells undergoing apoptotic cell death and p53 mutant/deleted cells having a mitotic catastrophe cell death. It mediates mitotic catastrophe mainly through Aurora B kinase. [4]
in vivo Buparlisib (BKM120) completely inhibits pAktser473 in A2780 xenograft tumors at doses of 30, 60, or 100 mg/kg, respectively, and also shows antitumor activity against U87MG glioma model at doses of 30 and 60 mg/kg. [1] This compound treatment results in significantly reduced tumor volume and level of circulating human kappa chain at 5 μM/kg/day−1 in ARP1 SCID mouse model, with prolonged survival. [2]

プロトコル(参考用のみ)

キナーゼアッセイ PI3K biochemical assay (ATP depletion assay)
Buparlisib (BKM120) is dissolved in DMSO and directly distributed into a black 384-well plate at 1.25 µL per well. To start the reaction, 25 µL of 10 nM PI3 kinase and 5 µg/mL 1-α-phosphatidylinositol (PI) in assay buffer (10 mM Tris pH 7.5, 5 mM MgCl2, 20 mM NaCl, 1 mM DTT and 0.05% CHAPS) are added into each well followed by 25 µL of 2 µM ATP in assay buffer. The reaction is performed until approx 50% of the ATP is depleted and then stopped by the addition of 25 µL of KinaseGlo solution. The stopped reaction is incubated for 5 minutes and the remaining ATP is then detected via luminescence.
細胞アッセイ 細胞株 A2780 cells.
濃度 0-6.6 μM
反応時間 3 days.
実験の流れ A2780 cells are cultured in DMEM supplemented with 10% FBS, L-glutamine, sodium pyruvate, and antibiotics. Cells are plated in the same medium at a density of 103 cells per well, 100 μL per well into black-walled-clear-bottom plates and incubated for 3-5 hours. Buparlisib (BKM120) supplied in DMSO (20 mM) is diluted. The diluted solution (2 μL) of this compound is then added to cell medium (500 μL) cell medium (concentration from 0-6.6 μM). Equal volumes of this solution (100 μL) are added to the cells in 96 well plates and incubated at 37 °C for 3 days and developed using Cell Titer Glo. Inhibition of cell proliferation is determined by luminescence read using Trilux.
動物実験 動物モデル U87MG and A2780 xenografts are established in female nu/nu mice.
投薬量 ~60 mg/kg.
投与方法 Dosed orally daily (q.d.).

参考

  • http://pubs.acs.org/doi/abs/10.1021/ml200156t
  • https://pubmed.ncbi.nlm.nih.gov/22207485/
  • https://pubmed.ncbi.nlm.nih.gov/22159814/
  • https://pubmed.ncbi.nlm.nih.gov/22065080/

カスタマーフィードバック

, , Mol Cancer Ther, 2017, 16(4):637-648

, , Dr. Zhang of Tianjin Medical University

Data independently produced by , , Dr. Pilar Eroles of INCLIVA Biomedical Research Institute.

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：

PPARα-mediated lipid metabolism reprogramming supports anti-EGFR therapy resistance in head and neck squamous cell carcinoma [ Nat Commun, 2025, 16(1):1237] PubMed: 39890801
PDE7A inhibition suppresses triple-negative breast cancer by attenuating de novo pyrimidine biosynthesis [ Cell Rep Med, 2025, 6(9):102356] PubMed: 40961924
Role of the PI3K/AKT signaling pathway in the cellular response to Tumor Treating Fields (TTFields) [ Cell Death Dis, 2025, 16(1):210] PubMed: 40148314
Enhancing Chemotherapeutic Efficacy in Lung Cancer Cells Through Synergistic Targeting of the PI3K/AKT Pathway with Small Molecule Inhibitors [ Int J Mol Sci, 2025, 26(17)8378] PubMed: 40943298
Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma [ Oncol Rep, 2025, 53(3)38] PubMed: 39886949
Low-Dose Perifosine, a Phase II Phospholipid Akt Inhibitor, Selectively Sensitizes Drug-Resistant ABCB1-Overexpressing Cancer Cells [ Biomol Ther (Seoul), 2025, 33(1):170-181] PubMed: 39632683
Dual inhibition of EGFR and PI3Kinase signaling in EGFR amplified triple negative breast cancer cells induces apoptosis and reduces tumor growth [ bioRxiv, 2025, 2025.06.03.657674] PubMed: 40501689
Exploiting an Epigenetic Resistance Mechanism to PI3 Kinase Inhibition in Leukemic Stem Cells [ bioRxiv, 2025, 2025.07.11.663968] PubMed: 40791365
Epidermal growth factor receptor specific immunotherapy for SHH medulloblastoma tested in an in vitro blood-brain barrier-model [ Cancer Treat Res Commun, 2025, 44:100950] PubMed: 40456204
Nf1 mutation disrupts activity-dependent oligodendroglial plasticity and motor learning in mice [ Nat Neurosci, 2024, 27(8):1555-1564.] PubMed: 38816530

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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