Pharmacokinetics and antineoplastic activity of galectin-1-targeting OTX008 in combination with sunitinib

Cancer Chemother Pharmacol. 2013 Oct;72(4):879-87. doi: 10.1007/s00280-013-2270-2. Epub 2013 Aug 24.


Purpose: OTX008 is a galectin-1-targeting compound, currently undergoing a phase I clinical trial. This study aimed at investigating OTX008 pharmacokinetics (PK) and antineoplastic activity.

Methods: Pharmacokinetics and activity of OTX008 were analyzed in the human ovarian carcinoma A2780-1A9 and glioblastoma U87MG xenografted in nude mice. In vitro, OTX008 was tested on tumor and endothelial cells.

Results: After 5 mg/kg i.v., OTX008 achieved plasma Cmax of 14.39 μg/mL, distributed rapidly, and was eliminated with a half-life of 31.4 h. Tumor OTX008 Cmax (1.65 μg/g, 1.76 μM), achieved at 0.5 h, remained high at 24 h (0.516 μg/g, 0.55 μM) with AUC of 15.76 μg/g*h. OTX008 accumulated in the tumor after repeated administrations achieving a concentration of 2.3 μM, compatible with the concentrations active in vitro. OTX008 (5 mg/kg i.v., every other day for 3 weeks) inhibited the in vivo growth of A2780-1A9, whereas U87MG was not sensitive. In vitro, OTX008 affected endothelial cell proliferation, motility, invasiveness, and cord formation. Tumor cell proliferation was also inhibited, with differences in sensitivity among cell lines (IC50 from 1 to 190 μM). OTX008 potentiated the activity of the tyrosine kinase inhibitor sunitinib on A2780-1A9 in vivo and in vitro, where the combination showed synergistic (endothelial cells) and additive (A2780-1A9) antiproliferative activity, indicating that the combination targets both the tumor and vascular compartments.

Conclusions: OTX008-alone or in combination with sunitinib-has a favorable PK and antineoplastic activity on selected tumor models through the effects on both endothelial and tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Area Under Curve
  • Calixarenes / administration & dosage
  • Calixarenes / pharmacokinetics
  • Calixarenes / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Synergism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Galectin 1 / metabolism*
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Half-Life
  • Humans
  • Indoles / administration & dosage
  • Inhibitory Concentration 50
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Pyrroles / administration & dosage
  • Sunitinib
  • Tissue Distribution
  • Xenograft Model Antitumor Assays


  • Galectin 1
  • Indoles
  • Pyrroles
  • compound 0118
  • Calixarenes
  • Sunitinib