PX-12 is an irreversible inhibitor of thioredoxin (Trx-1), a protein that regulates many transcription factors including hypoxia inducible factor (HIF)-1 alpha, vascular endothelial growth factor (VEGF) and activator protein 1 (AP-1). These factors play a critical role in cancer cell growth, survival and resistance to chemotherapy. Increased thioredoxin levels in cancer cells have been linked to the aggressive proliferation of solid tumors, including colon, lung, and gastric cancers. PX-12 has successfully completed Phase I safety evaluation and is currently being studied in a Phase 2 trial in patients with advanced pancreatic cancer. An initial Phase I trial involving 38 patients with advanced metastatic cancer showed that PX-12 was well tolerated and produced a decrease in plasma concentrations of thioredoxin that was significantly correlated with increased patient survival. Fifteen of the 38 patients achieved stable disease of up to 322 days.
PX-866 is an inhibitor of the phosphatidylinositol-3-kinase (PI3 kinase)/PTEN/AKT pathway, an important survival signaling pathway that is activated in many types of human cancer. PI3 kinase is overexpressed in a number of human cancers, especially ovarian, colon, head and neck, urinary tract, and cervical cancers, where it leads to increased proliferation and inhibition of apoptosis (programmed cell death). In preclinical studies, PX-866 has been shown to induce prolonged inhibition of tumor PI3 kinase signaling following both oral and intravenous administration. The compound also has been shown to have good in vivo anti-tumor activity in tumor models of human ovarian and lung cancer, as well as intracranial glioblastoma. Oncothyreon expects to file an Investigational New Drug application for PX-866 in the current quarter of 2008.
Oncothyreon is a biotechnology company specializing in the development
|SOURCE Oncothyreon Inc.|
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