| CAS |
No.944396-07-0 |
| 中文名称 |
布帕尼西 |
| 英文名称 |
Buparlisib |
| 别名 |
BKM120 |
| 分子式 |
C18H21F3N6O2 |
| 分子量 |
410.39 |
| 溶解性 |
Soluble in DMSO(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD18251596 |
| SMILES |
C1COCCN1C2=NC(=NC(=C2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4 |
| InChIKey |
CWHUFRVAEUJCEF-UHFFFAOYSA-N |
| InChI |
InChI=1S/C18H21F3N6O2/c19-18(20，21)13-9-15(22)23-11-12(13)14-10-16(26-1-5-28-6-2-26)25-17(24-14)27-3-7-29-8-4-27/h9-11H，1-8H2，(H2，22，23) |
| PubChem CID |
16654980 |
| 靶点 |
PI3K |
| 通路 |
PI3K/Akt/mTOR |
| 背景说明 |
Buparlisib 是一种选择性 PI3K 抑制剂。 |
| 生物活性 |
Buparlisib (BKM120; NVP-BKM120) is a pan-class I PI3K inhibitor， with IC50s of 52， 166， 116 and 262 nM for p110α， p110β， p110δ and p110γ， respectively.[1-4] |
| In Vitro |
Buparlisib (NVP-BKM120) exhibits 50-300 nM activity for class I PI3K’s， including the most common p110α mutants. Additionally， NVP-BKM120 exhibits lower potency against class III and class IV PI3K‘s， where 2， 5， >5， and >25 μM biochemical activity is observed for inhibition of VPS34， mTOR， DNAPK， and PI4K， respectively[1]. Buparlisib (NVP-BKM120) induces multiple myeloma (MM) cell apoptosis in both dose- and time-dependent manners. Buparlisib (NVP-BKM120) at concentrations ≥10 μM induces significant apoptosis in all tested MM cell lines at 24 h (P50 varies among tested MM cells. At 24 h treatment， IC50 for ARP-1， ARK， and MM.1R is between 1 and 10 μM， while IC50 for MM.1S is 50 for U266 is between 10 and 100 μM. In summary， NVP-BKM120 treatment results in MM cell growth inhibition and apoptosis in dose- and time-dependent manners[2]. |
| In Vivo |
In A2780 xenograft tumors， oral dosing of Buparlisib (NVP-BKM120) at 3， 10， 30， 60， and 100 mg/kg results in a dose dependent modulation of pAKTSer473. Partial inhibition of pAKTSer473 is observed at 3 and 10 mg/kg， and near complete inhibition is observed at doses of 30， 60， or 100 mg/kg， respectively. Inhibition of pAKT (normalized to total AKT) tracked well with both plasma and tumor drug exposure[1]. Mice receiving Buparlisib (NVP-BKM120) (5 μM per kg per day for 15 days) treatment has significantly smaller tumor burdens as compare with control mice， which are measured as tumor volume (P[2]. |
| 细胞实验 |
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 1000 cells per well， 100 uL per well into black-walled-clear-bottom plates and incubated for 3-5 hours. Buparlisib (NVP-BKM120) supplied in DMSO (20 mM) are diluted further into DMSO (7.5 uL of 20 mM Buparlisib (NVP-BKM120) in 22.5 uL DMSO. Mix well， transfer 10 uL to 20 uL DMSO， repeat until 9 concentrations have been made). The diluted Buparlisib (NVP-BKM120) solution (2 uL)， is then added to cell medium (500 uL) cell medium. Equal volumes of this solution (100 uL) are added to the cells in 96 well plates and incubated at 37oC for 3 days and developed using Cell Titer Glo. Inhibition of cell proliferation is determined by luminescence read using Trilux[1]. |
| 动物实验 |
Mice[2] Six- to eight-week-old female severe combined immunodeficiency (SCID) mice are used. SCID mice are subcutaneously inoculated in the right flank with 1 million ARP-1 or MM.1S cells suspended in 50 μL phosphate-buffered saline (PBS). After palpable tumor developed (tumor diameter ≥5 mm)， mice are treated with intraperitoneal injection of DMSO/PBS or Buparlisib (NVP-BKM120) (5 μM per kg per day) for 15 days. Tumor sizes are measured every 5 days， and blood samples are collected at the same period. Tumor burdens are evaluated by measuring tumor size and detecting circulating human kappa chain or lambda chain. |
| 数据来源文献 |
[1]. Burger MT， 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 Aug 26;2(10):774-9.
[2]. Zheng Y， et al. Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergistic anti-myeloma activity. J Mol Med (Berl). 2012 Jun;90(6):695-706.
[3]. Ni J， et al. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nat Med. 2016 Jul;22(7):723-6.
[4]. Liu H， et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Cancer Discov. 2018 Mar;8(3):354-369. |
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