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Buparlisib

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Chemical Structure| 944396-07-0 同义名 : BKM120;NVP-BKM120
CAS号 : 944396-07-0
货号 : A105286
分子式 : C18H21F3N6O2
纯度 : 98%
分子量 : 410.394
MDL号 : MFCD18251596
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(255.85 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5% DMSO+30% PEG 300+water 15 mg/mL

生物活性
靶点

  • p110γ

    p110γ, IC50:262 nM

  • p110β

    p110β, IC50:166 nM

  • p110α

    p110α, IC50:52 nM

  • p110δ

    p110δ, IC50:116 nM

  • Vps34

    Vps34, IC50:2.4 μM
描述 PI3Ks (Phosphatidylinositol-4,5-bisphosphate 3-kinase) participate in a diverse array of process, including the regulation of cellular survival, differentiation and stem cell-like properties, growth, proliferation, metabolism, migration, and angiogenesis[2]. BKM120 is an orally bioavailable pan-PI3K inhibitor with IC50 value of IC50=52nM, IC50=116nM, IC50=166nM, IC50=262nM, IC50=2.4μM, IC50=4.6μM on p110α, p110δ, p110β, p110γ(measured by filter binding assay), Vps34 (measured by ATP depletion assay), mTOR (measured by TR-FRET assay), respectively, most potent on Class I PI3Ks. Treatment of BKM120 can cause decrease of p-AKT-ser473 (downstream of PI3Ks) both in vitro and in vivo. BKM120 has good pharmacokinetic properties, exhibiting medium to high oral bioavailability across species as 80%, 50%, 44% and 100% observed in mouse, rat, dog, and monkey, respectively[1]. For BKM120 is well-tolerated and permeable to the blood–brain barrier, it is the most frequently-used PI3K inhibitor in the clinical trials for glioblastoma multiforme treatment[3].
作用机制 Mechanism: BKM120 has greater affinity for the free PI3K enzyme,relative to the ATP bound.[4]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
786-0 1-20μM Growth Inhibition Assay 72h IC50＜1μM 23479136
A2780 Cytotoxic Assay 72 h Cytotoxicity against PTEN-deficient human A2780 cells with GI50 of 0.000635 μM 24900266
A2780 Function Assay 1 h Inhibition of PI3K-mediated AKT Ser473 phosphorylation with EC50 of 0.055 μM 24900266
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01820364 Melanoma Phase 2 Terminated(Study was withdrawn... 展开 >> due to scientific and business considerations.) 收起 << - United States, Tennessee ... 展开 >> Sarah Cannon Research Institute Onc Dept Nashville, Tennessee, United States, 37203 Australia, Victoria Novartis Investigative Site East Melbourne, Victoria, Australia, 3002 Canada, Alberta Novartis Investigative Site Edmonton, Alberta, Canada, T6G 1Z2 Germany Novartis Investigative Site Heidelberg, Germany, 69120 Spain Novartis Investigative Site Barcelona, Catalunya, Spain, 08035 Switzerland Novartis Investigative Site Zuerich, Switzerland, 8091 收起 <<
NCT01820364 - Terminated(Study was withdrawn... 展开 >> due to scientific and business considerations.) 收起 << - -
NCT02159066 Melanoma Phase 2 Active, not recruiting March 30, 2019 United States, Arizona ... 展开 >> Mayo Clinic - Arizona onc Dept Scottsdale, Arizona, United States United States, California University of California at Los Angeles Onc Dept Los Angeles, California, United States, 90095 United States, Massachusetts Massachusetts General Hospital Dept of Onc. Boston, Massachusetts, United States, 02115 United States, New York Memorial Sloan Kettering Cancer Center Dept Oncology New York, New York, United States, 90033 United States, Oregon Oregon Health & Science University Onc. Dept Portland, Oregon, United States, 97239 United States, Tennessee Sarah Cannon Research Institute Onc. Dept Nashville, Tennessee, United States, 37203 Australia, Victoria Array BioPharma Investigative Site East Melbourne, Victoria, Australia, 3002 Canada, Ontario Array BioPharma Investigative Site Toronto, Ontario, Canada, M5G 2M9 Canada, Quebec Array BioPharma Investigative Site Montreal, Quebec, Canada, H3T 1E2 Germany Array BioPharma Investigative Site Heidelberg, Germany, 69120 Array BioPharma Investigative Site Köln, Germany, 50937 Array BioPharma Investigative Site Muenchen, Germany, 80336 Array BioPharma Investigative Site Würzburg, Germany, 97080 Italy Array BioPharma Investigative Site Napoli, Italy, 80131 Netherlands Array BioPharma Investigative Site Amsterdam, Netherlands, 1066 CX Spain Array BioPharma Investigative Site Barcelona, Catalunya, Spain, 08035 Switzerland Array BioPharma Investigative Site Zuerich, Switzerland, 8091 United Kingdom Array BioPharma Investigative Site Oxford, United Kingdom, OX3 7LJ 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.44mL

0.49mL

0.24mL

12.18mL

2.44mL

1.22mL

24.37mL

4.87mL

2.44mL
参考文献

[1]Burger MT, Pecchi S, et al. Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer. ACS Med Chem Lett. 2011;2(10):774-9.

[2]Vanhaesebroeck B, Guillermet-Guibert J, et al. The emerging mechanisms of isoform-specific PI3K signalling. Nat Rev Mol Cell Biol. 2010;11(5):329-41.

[3]Zhao HF, Wang J, et al. Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development. Mol Cancer. 2017;16(1):100.

[4]Maira SM, Pecchi S, et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther. 2012;11(2):317-28.

[5]Speranza MC, Nowicki MO, et al. BKM-120 (Buparlisib): A Phosphatidyl-Inositol-3 Kinase Inhibitor with Anti-Invasive Properties in Glioblastoma. Sci Rep. 2016 Feb 5;6:20189.