GFB-204
Mechanism of Action and Preclinical Development
GFB-204 is a calixarene derivative that is a potent and selective inhibitor of VEGFR and PDGFR tyrosine phosphorylation. GFB-204 had been shown through several in-vivo and in-vitro studies to bind to VEGF and PDGF, block binding of VEGF and PDGF to their receptors and subsequently inhibit Flk-1 and PDGFR tyrosine phosphorylation and stimulation of the protein kinases Erk1, Erk2, and AKT and the signal transducer and activator of transcription STAT3. Since tumor angiogenesis depends on VEGF for initiation and PDGF for maintenance of blood vessels, an agent which suppresses the functions of both VEGF and PDGF would potentially be more effective in tumor control that an agent which targets only one of these two growth factors.
Preclinical studies have also shown that GFB-204 inhibits capillary network formation in a dose-response manner and inhibits VEGF-dependent human brain endothelial cell migration. A lung xenograft study in mice has shown that GFB-204 is active in a dose dependent manner.
Clinical Development
Tigris Pharmaceuticals in currently completing preclinical IND enabling studies and is planning to initiate Phase I studies to evaluate GFB-204 as a potential cancer therapeutic in patients with a variety of solid tumors upon IND acceptance.
Publications
- Sun J, Wang D, Jain R, et al., Inhibiting angiogenesis and tumorigenesis by a synthetic molecule that blocks binding of both VEGF and PDGF to their receptors. Oncogene, 2005.
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