生物活性

• 靶点

  Bromodomain 4 IC50:25nM

  PLK1 IC50:0.83nM

• 描述Polo-like kinase 1 (Plk1) is a serine/theonin-specific kinase that regulates multiple stages during mitotic progression and acts as a negative prognostic marker in different types of human cancers. BI-2536 is a Plk1 inhibitor that blocks human Plk1 with an IC50 value of 0.83 nM. It also inhibits the activities of Plk2 and Plk3 with IC50 values of 3.5 nM and 9.0 nM, respectively. Accumulated 4N DNA content was observed in HeLa-S3 cells treated by BI-2536 (10 nM – 1 μM) for 24 hours, indicating a blockage of cell-cycle. When HeLa cells synchronized at the G1/S transition were treated with 60 nM BI-2536, cells released into median progressed through S phase normally followed by the G2/M arrest. In hTERT-RPE1 cells treated by BI-2536 (100 nM), nearly 70% of mitotic cells demonstrated a typical “Polo” phenotype. Intravenous injection of BI-2536 (40 – 50 mg/kg, once or twice/week) for 20 - 30 days inhibited the growth of HCT 116 tumor xenografts in immunodeficient, nu/nu mice. In a more rigorous xenograft model of larger HCT 116 tumors, 5 cycles of BI-2536 (50 mg/kg, twice weekly on two consecutive days) efficiently induced tumor regressions compared to control mice. In addition, four to seven cycles of BI-2536 (50 mg/kg, twice weekly on two consecutive days) also inhibited tumor growth in BxPC-3 and A549 xenograft models with T/C values of 5% and 14%, respectively. BI-2536 also inhibited the growth of NCI-H460 lung carcinomas, increased mitotic index and histone H3 phosphorylation in nu/nu mice)^[3].
• 作用机制BI-2536 is derived from a chemical series, the dihydro-pteridinones, and functions as an ATP-competitive inhibitor for Plk1^[3].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  5637	-	Growth Inhibition Assay	-	IC50=45.47 nM	23792639
  697	-	Growth Inhibition Assay	-	IC50=0.01668 μM	SANGER
  697	-	Growth Inhibition Assay	24 h	IC50=2107.1 nM	24519995

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• 动物研究
  剂量	Nude Mice: 40 mg/kg - 50 mg/kg[3] (i.v.); 10 mg/kg, 20 mg/kg[4] (i.p.)
  给药途径	i.v., i.p.

• 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
  NCT00526149	Breast Cancer ... more >> Endometrial Cancer Head and Neck Cancer Melanoma (Skin) Ovarian Cancer Sarcoma Collapse <<	Phase 2	Completed	-	Belgium ... more >> U.Z. Gasthuisberg Leuven, Belgium, B-3000 Collapse <<
  NCT00710710	Pancreatic Neoplasms	Phase 2	Completed	-	Austria ... more >> 1216.10.43001 Boehringer Ingelheim Investigational Site Wien, Austria Germany 1216.10.49013 Boehringer Ingelheim Investigational Site Celle, Germany 1216.10.49009 Boehringer Ingelheim Investigational Site Düsseldorf, Germany 1216.10.49007 Boehringer Ingelheim Investigational Site Essen, Germany 1216.10.49001 Boehringer Ingelheim Investigational Site Freiburg/Breisgau, Germany 1216.10.49005 Boehringer Ingelheim Investigational Site Hamburg, Germany 1216.10.49010 Boehringer Ingelheim Investigational Site Herne, Germany 1216.10.49008 Boehringer Ingelheim Investigational Site München, Germany 1216.10.49003 Boehringer Ingelheim Investigational Site Stuttgart, Germany 1216.10.49002 Boehringer Ingelheim Investigational Site Ulm, Germany Collapse <<
  NCT00412880	Carcinoma, Small Cell	Phase 2	Completed	-	United States, Arkansas ... more >> 1216.11.007 Boehringer Ingelheim Investigational Site Fayetteville, Arkansas, United States United States, Illinois 1216.11.003 Boehringer Ingelheim Investigational Site Chicago, Illinois, United States 1216.11.006 Boehringer Ingelheim Investigational Site Evanston, Illinois, United States United States, Massachusetts 1216.11.002 Boehringer Ingelheim Investigational Site Boston, Massachusetts, United States United States, Missouri 1216.11.005 Boehringer Ingelheim Investigational Site St. Louis, Missouri, United States United States, North Carolina 1216.11.001 Boehringer Ingelheim Investigational Site Chapel Hill, North Carolina, United States United States, South Carolina 1216.11.011 Boehringer Ingelheim Investigational Site Charleston, South Carolina, United States 1216.11.010 Boehringer Ingelheim Investigational Site Greenville, South Carolina, United States United States, Washington 1216.11.012 Boehringer Ingelheim Investigational Site Seattle, Washington, United States Canada, Alberta 1216.11.009 Alberta Cancer Board Edmonton, Alberta, Canada Collapse <<

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