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Synonyms | NVP-BKM120 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C18H21F3N6O2 |
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分子量 | 410.39 | CAS No. | 944396-07-0 | |
Solubility (25°C)* | 体外 | DMSO | 82 mg/mL (199.8 mM) | |
Ethanol | 16 mg/mL (38.98 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. |
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. |
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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] |
キナーゼアッセイ | PI3K biochemical assay (ATP depletion assay) | |
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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.). |
, , 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.
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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