生物活性

• 靶点	FAK IC50:1.5nM

• 描述FAK (focal adhesion kinase), a cytoplasmic non-receptor protein-tyrosine kinase, is associated with tumor progression through its modulation of various cellular processes including growth, survival, and migration. PND-1186 is reversible FAK inhibitor with IC50 value of 1.5 nM (measured by purified FAK kinase activity). It had IC50 value of about 100 nM for inhibition of p-FAK-Y397 in breast carcinoma cells. Exposure to 1 μM PND-1186 for 22 h restrains 4T1 breast carcinoma motility with only 40% closure, but no cell detachment or death observed, in wound healing assays. Low-concentration treatment with PND-1186 at 0.1-1 μM for 24-72 h caused dose- and time-dependent increased apoptosis of 4T1 cells cultured in suspension, but not under adherent condition. Consistent with this, PND-1186 could reduce the spheroid size of 3D-cultured 4T1 cells for 3 fold at concentration of 0.1 μM for 72 h with maximal effects achieved at 0.2 μM, which may due to the inhibition of tyrosine phosphorylation of both FAK and p130Cas under spheroid growth conditions but not 2D culture. Oral administration of PND-1186 at 100 mg/kg, BID, for 5 days inhibited 4T1 subcutaneous tumor growth in mice through induction of apoptosis^[1].

• 动物研究
  剂量	Mice: 30 mg/kg, 100 mg/kg[2] (s.c.)
  给药途径	s.c.

• 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
  NCT01849744	Non Hematologic Cancers ... more >> Metastatic Cancer Collapse <<	Phase 1	Terminated(Sponsor's decision ... more >>to deprioritize the program.) Collapse <<	-	United States, Arizona ... more >> HonorHealth Research Institute Scottsdale, Arizona, United States, 85258 United States, California Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center Los Angeles, California, United States, 90048 United States, Florida Florida Cancer Specialists Sarasota, Florida, United States, 34232 United States, Missouri Washington University School of Medicine, Division of Oncology Saint Louis, Missouri, United States, 63110 United States, Tennessee Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203 Collapse <<
  NCT02651727	Pancreatic Cancer	Phase 1	Terminated(the company's decis... more >>ion to de-prioritize 4718 development) Collapse <<	-	United States, Missouri ... more >> Washington University School of Medicine Saint Louis, Missouri, United States, 63110 United States, Pennsylvania Gettysburg Cancer Center Gettysburg, Pennsylvania, United States, 17325 Collapse <<
  NCT02215629	Relapsed or Refractory Acute M... more >>yeloid Leukemia Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia Collapse <<	Phase 1	Withdrawn	November 2016	-

• 参考文献