生物活性

• 靶点	PLK1 IC50:0.87nM

• 描述BI 6727 is a highly potent PLK inhibitor with IC50 values of 0.87nM, 5nM and 56nM for PLK1, 2 and 3, respectively. Volasertib inhibited proliferation of multiple cell lines with EC50 values of 23nM, 21nM, 11nM, 15nM, 32nM, 36nM and 37nM for HCT 116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1 and Raji cell line, respectively. BI 6727 induced apoptosis, shown by cleaved PARP, in NCI-H460 cells at 100nM post 24h and 48h. An accumulation of mitotic cells with monopolar spindles and positive staining for histone H3 phosphoserine 10 of NCI-H460 cells could also be observed post BI 6727 treatment, confirming that cells are arrested early in the M phase. It exhibited marked antitumor activity in multiple cancer models, including models xenograft HCT 116, NCI-H460 and CXB1 15 cells as well as a model of taxane-resistant colorectal cancer, with oral and i.v. routes of administration at doses ranging in 7-70mg/kg.
• 作用机制BI 6727 binds in the ATP binding pocket of Plk1.^[1]
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  5637	-	Growth Inhibition Assay	48 h	IC50=1165.14 nM	23792639
  A431	0-30 nM	Growth Inhibition Assay	1-4 d	inhibits cell growth in both dose- and time-dependent manner	23891096
  BRO	-	Growth Inhibition Assay	-	EC50 = 11 nM	19383823

• 更多

• 动物研究
  剂量	Mice: 30 mg/kg[2] (i.v.), 40 mg/kg[1] (i.v.), 50 mg/kg[1] (p.o.) Rat: 10 mg/kg[1] (i.v.), 30 mg/kg[1] (p.o.)
  给药途径	i.v., p.o.
  动物药代数据	Animal Mice[1] Rats[1] Dose 35 mg/kg (i.v.) 50 mg/kg (p.o.) 10 mg/kg (i.v.) 30 mg/kg (p.o.) Administration i.v. p.o. i.v. p.o. F 41% (p.o.) 55% (p.o.) AUC0→inf 100 µmol·h/l (i.v.) T1/2 46 h (i.v.) 54 h (i.v.) Tmax 1.7 h (p.o.) 6.7 h (p.o.) AUC0-inf 30 µmol·h/l (i.v.) CL 10 ml/min/kg (i.v.) 8.9 ml/min/kg (i.v.) Cmax 7.1 µmol/l (i.v.) 5.7 µmol/l (p.o.) 11.9 µmol/l (i.v.) 2.2 µmol/l (p.o.) Vss 7.6 L/kg (i.v.) 22 L/kg (i.v.) AUC0→24h 58 µmol·h/l (p.o.) 34 µmol·h/l (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
  NCT01023958	Neoplasms	Phase 2	Completed	-	United States, California ... more >> 1230.2.5 Boehringer Ingelheim Investigational Site Beverly Hills, California, United States 1230.2.10 Boehringer Ingelheim Investigational Site Los Angeles, California, United States United States, Florida 1230.2.34 Boehringer Ingelheim Investigational Site Miami, Florida, United States 1230.2.29 Boehringer Ingelheim Investigational Site Orlando, Florida, United States United States, Illinois 1230.2.6 Boehringer Ingelheim Investigational Site Chicago, Illinois, United States 1230.2.17 Boehringer Ingelheim Investigational Site Joliet, Illinois, United States United States, Louisiana 1230.2.24 Boehringer Ingelheim Investigational Site Metairie, Louisiana, United States United States, Maryland 1230.2.1 Boehringer Ingelheim Investigational Site Baltimore, Maryland, United States United States, Nevada 1230.2.25 Boehringer Ingelheim Investigational Site Las Vegas, Nevada, United States 1230.2.36 Boehringer Ingelheim Investigational Site Las Vegas, Nevada, United States United States, New Hampshire 1230.2.19 Boehringer Ingelheim Investigational Site Lebanon, New Hampshire, United States United States, New York 1230.2.20 Boehringer Ingelheim Investigational Site New York, New York, United States 1230.2.23 Boehringer Ingelheim Investigational Site New York, New York, United States United States, North Carolina 1230.2.12 Boehringer Ingelheim Investigational Site Charlotte, North Carolina, United States United States, Pennsylvania 1230.2.4 Boehringer Ingelheim Investigational Site Philadelphia, Pennsylvania, United States United States, Texas 1230.2.38 Boehringer Ingelheim Investigational Site Beaumont, Texas, United States 1230.2.41 Boehringer Ingelheim Investigational Site Tyler, Texas, United States 1230.2.43 Boehringer Ingelheim Investigational Site Webster, Texas, United States United States, Virginia 1230.2.44 Boehringer Ingelheim Investigational Site Fairfax, Virginia, United States Taiwan 1230.2.51 Boehringer Ingelheim Investigational Site Tainan, Taiwan 1230.2.50 Boehringer Ingelheim Investigational Site Taipei, Taiwan Collapse <<
  NCT00969553	Neoplasms	Phase 1	Completed	-	Taiwan ... more >> 1230.16.886002 Boehringer Ingelheim Investigational Site Tainan, Taiwan 1230.16.886001 Boehringer Ingelheim Investigational Site Taipei, Taiwan Collapse <<
  NCT01023958	-	-	Completed	-	-

• 更多
• 参考文献

• [1] Rudolph D, Steegmaier M, et al. BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity. Clin Cancer Res. 2009 May 1;15(9):3094-102.

  [2] Gorlick R, Kolb EA, et al. Initial testing (stage 1) of the Polo-like kinase inhibitor volasertib (BI 6727), by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2014 Jan;61(1):158-64.