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
* <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 BKM120 is not sensitive to Class III and Class IV PI3K's or PI4K. NVP-BKM120 shows great antiproliferation activity to PI3K deregulated cell lines including A2780, U87MG, MCF7 and DU145 with GI50 of 0.1-0.7 nM. [1] BKM120 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. BKM120 induced CD138+ primary MM cell apoptosis and has significant lower cytotoxicity toward CD138− stromal cells. BKM120 exposure could cause upregulation of BimS and downregulation of XIAP. [2] BKM120 demonstrates antiproliferative activity in human gastric cancer cell lines by decreasing mTOR downstream signaling. BKM120 could increase either p-ERK or p-STAT3 in KRAS mutant gastric cancer cells. Combination with STAT3 blockade, BKM120 shows a synergism in cells harboring mutated KRAS by inducing apoptosis, but not in KRAS wild-type cells. [3] A recent study shows that BKM120 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. BKM120 mediates mitotic catastrophe mainly through Aurora B kinase. [4]
in vivo BKM120 completely inhibits pAktser473 in A2780 xenograft tumors at doses of 30, 60, or 100 mg/kg, respectively. BKM120 also shows antitumor activity against U87MG glioma model at doses of 30 and 60 mg/kg. [1] BKM120 treatment results in significantly reduced tumor volume and level of circulating human kappa chain at 5 μM/kg/day−1in 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)
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. BKM120 supplied in DMSO (20 mM) is diluted. The diluted BKM120 solution (2 μL), 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.).

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：

METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer [ Mol Cancer, 2023, 22(1):119] PubMed: 37516825
Stellettin B Sensitizes Glioblastoma to DNA-Damaging Treatments by Suppressing PI3K-Mediated Homologous Recombination Repair [ Adv Sci (Weinh), 2023, 10(3):e2205529] PubMed: 36453577
HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway by regulating MSK1 and PPP2R2B [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101285] PubMed: 37951219
ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias [ Blood Cancer J, 2023, 13(1):42] PubMed: 36959186
Cytoskeletal association of ATP citrate lyase controls the mechanodynamics of macropinocytosis [ Proc Natl Acad Sci U S A, 2023, 120(8):e2213272120] PubMed: 36787367
Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells [ Cell Rep, 2023, 42(5):112529] PubMed: 37200193
LTK and ALK promote neuronal polarity and cortical migration by inhibiting IGF1R activity [ EMBO Rep, 2023, 24(7):e56937] PubMed: 37291945
FLI1 regulates radiotherapy resistance in nasopharyngeal carcinoma through TIE1-mediated PI3K/AKT signaling pathway [ J Transl Med, 2023, 21(1):134] PubMed: 36814284
Combined BCL-2 and PI3K/AKT Pathway Inhibition in KMT2A-Rearranged Acute B-Lymphoblastic Leukemia Cells [ Int J Mol Sci, 2023, 24(2)1359] PubMed: 36674872
PI5P4Kα supports prostate cancer metabolism and exposes a survival vulnerability during androgen receptor inhibition [ Sci Adv, 2023, 9(5):eade8641] PubMed: 36724278

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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