生物活性

• 靶点

  ATR IC50:21nM

  mTOR(p70S6K) IC50:6nM

  p110α IC50:4nM

  p110β IC50:75nM

  p110γ IC50:5nM

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• 描述Aberrant activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin inhibitor (mTOR) signaling pathway promotes the proliferation and survival of various human tumor cells. BEZ235 is a ATP competitive inhibitor of PI3K that inhibits the kinase activity of Class I PI3K p110α/β/δ/γ with IC50 of 4 nM, 75 nM, 7 nM, and 5 nM, respectively. In U87MG glioblastoma cells, the exposure of 0.1 - 1000 nM BEZ235 for 30 min reduced S473P-Akt and T308P-Akt levels in a dose-dependent manner, and the 50% reduction occurred at the doses of 8 nM and 30 nM, respectively. In NWT21 cells, pretreatment of 250 nM BEZ235 reduced insulin-like growth factor-I-induced S473P-Akt level. In starved HT-29 cells, BEZ235 at 250 nM efficiently inhibited interleukin-4-induced S473P-Akt level. The phosphorylation level of mTOR activated kinase p70^S6K was significantly reduced by 250 nM BEZ235 in U87MG cells after 30 min incubation. The S235/S236P-RPS6 level in TSC1-null MEF cells was decreased by BEZ235 with an IC50 of 6.5 nM. The addition of BEZ235 (5 - 500 nM) dose-dependently downregulated mTORC1 and mTORC2 activities in IgG-Sepharose pull-downs of HeLa cells. BEZ235 also showed inhibitory effect on cell proliferation. The G_{1 population of PC3M cells was increased from 66.4% to 74.1% and 92.3% after the treatment with 10 nM and 50 nM BEZ235, respectively. In U87MG tumor-bearing mice, treatment of BEZ235 (25 – 45 mg/kg/d, once daily) for 20 days inhibited tumor growth and reduced S473P-Akt levels in the tumor at a dose-dependent manner^[3].}
• 作用机制BEZ235 inhibits PI3K via binding to its ATP-binding cleft^[3].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  A3-KAW	-	Growth Inhibition Assay	-	IC50=28.64 nM	SANGER
  A427	-	Growth Inhibition Assay	-	IC50=182.57 nM	SANGER
  A431	-	Growth Inhibition Assay	-	IC50=89.97 nM	SANGER

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• 动物研究
  剂量	Mice[3] (p.o.): min = 1 mg/kg, max = 50 mg/kg
  给药途径	p.o.

• 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
  NCT01285466	Metastatic or Locally Advanced... more >> Solid Tumors Collapse <<	Phase 1	Completed	-	Belgium ... more >> Novartis Investigative Site Bruxelles, Belgium, 1000 Novartis Investigative Site Bruxelles, Belgium, 1200 Novartis Investigative Site Wilrijk, Belgium, 2610 Germany Novartis Investigative Site Essen, Germany, 45147 Novartis Investigative Site Köln, Germany, 50937 Netherlands Novartis Investigative Site Amsterdam, Netherlands, 1066 CX Spain Novartis Investigative Site Sevilla, Andalucia, Spain, 41013 Novartis Investigative Site Barcelona, Catalunya, Spain, 08035 Switzerland Novartis Investigative Site Chur, Switzerland, 7000 Novartis Investigative Site St. Gallen, Switzerland, 9007 Collapse <<
  NCT02430363	Glioblastoma	Phase 1 Phase 2	Unknown	June 2018	United States, Massachusetts ... more >> Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, Texas M D Anderson Cancer Center Houston, Texas, United States, 77030 Belgium UCL- Cliniques Universitaires Saint Luc Brussels, Belgium Germany St Johannes Hospital Duisburg, Germany, 47166 Italy Spedali Civili di Brescia Brescia, Italy IRCCS San Raffaele Milan, Italy Poland Lower-Silesian Oncology Centre Wroclaw, Lower-Silesian, Poland, 53413 Russian Federation Pavlov State Medical University St. Petersburg, Russian Federation, 197089 Spain Hospital Universitario Germans Trias I Pujol Barcelona,, Spain Switzerland Universitätsklinik für Frauenheilkunde Bern, Switzerland Ukraine Regional Cancer Center Dnepropetrovsk, Ukraine, 49000 National Institute of Cancer Kiev, Ukraine, 03035 United Kingdom Royal Victoria Hospital Belfast, Ulster, United Kingdom, BT12 6BA Collapse <<
  NCT01508104	Cancer	Phase 1	Terminated(funding)	-	United States, Ohio ... more >> University of Cincinnati Cincinnati, Ohio, United States, 45267-0502 Collapse <<

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