Vascular endothelial growth factor receptor tyrosine kinase inhibitors: PTK787/ZK 222584

Vascular Endothelial Growth Factor (VEGF), VEGF Receptors and Their Inhibitors for Antiangiogenic Tumor Therapy

“…In addition, vatalanib (PTK787, ZK222584) suppresses the kinase activities of VEGFR, platelet-derived growth factor receptor and c-kit, and is under clinical investigation for the treatment of metastatic colorectal cancer. 48,51) Aflibercept (AVE0005) is a soluble fusion protein of the extracelluar domain of human VEGFR-1 and VEGFR-2 and the Fc region of IgG, and is also called VEGF-Trap. 52) Aflibercept prevents VEGFR activation and downstream signaling because it efficiently binds VEGF-A and PlGF with high affinity.…”

Hypoxia and Angiogenesis in Pancreatic Cancer

“…This effect was potentiated by using a combination therapy with PKI‐166 and gemcitabine 144,145 . PTK‐787/ZK222584 has progressed through preclinical evaluation in gastrointestinal tumour models and is currently undergoing Phase I clinical trials, where preliminary data suggest that it is well tolerated with surrogate end‐point evidence of a biological response 146 . A combination of PTK‐787 and gemcitabine in mice models of pancreatic cancer resulted in 81% inhibition of the volume of pancreatic tumours, with a decrease incidence in lymph node invasion and hepatic metastases 147 …”

Green tea catechins inhibit angiogenesis through suppression of STAT3 activation

“…Among these agents are monoclonal VEGF antibodies, small-molecule inhibitors of VEGFR, and several natural products that exhibit antiangiogenic properties including milk thistle, turmeric, ginger, and green tea [6–11]. Unlike single antiangiogenic agents, natural products often exert actions on several signaling pathways besides angiogenesis, including proliferation and apoptosis.…”