Buparlisib (BKM120)

Catalog No.S2247 Batch:S224702

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Technical Data

Formula

C18H21F3N6O2
Molecular Weight 410.39 CAS No. 944396-07-0
Solubility (25°C)* In vitro DMSO 82 mg/mL (199.8 mM)
Ethanol 25 mg/mL (60.91 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description 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.
Targets
p110α [1]
(Cell-free assay)		 p110δ [1]
(Cell-free assay)		 p110β [1]
(Cell-free assay)		 p110γ [1]
(Cell-free assay)		 Vps34 [1]
(Cell-free assay)		 View More
52 nM 116 nM 166 nM 262 nM 2.4 μM
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[1]
  • Cell lines

    A2780 cells.

  • Concentrations

    0-6.6 μM

  • Incubation Time

    3 days.

  • Method

    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.
Animal Study:[1]
  • Animal Models

    U87MG and A2780 xenografts are established in female nu/nu mice.

  • Dosages

    ~60 mg/kg.

  • Administration

    Dosed orally daily (q.d.).

Customer Product Validation

, , 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.

, , One customer

Selleck's Buparlisib (BKM120) has been cited by 277 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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