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Description
Oncothyreon's lead compound targeting thioredoxin signaling is PX-12, a small molecule currently in a Phase 2 clinical trial. PX-12 is designed inhibit the activity of thioredoxin-1 (Trx-1) through irreversibly binding to the protein. Inhibition of Trx-1 by PX-12 has been shown at low micromolar concentrations in culture and results in potent stimulation of apoptosis. This inhibition also causes inhibition of tumor growth in animals.
PX-12 Inhibits Thioredoxin-1(Trx-1) Activity
- Trx-1 regulates transcription factor activity and inhibits apoptosis inside the cell, promoting cell growth and survial
- Trx-1 interacts with growth factors (GF) outside the cell to stimilate cell growth
- Trx-1 overexpression is linked to aggressive tumor growth and poor prognosis
- PX-12 irreversibly binds to Trx-1 inhibiting growth and inducing apoptosis of cells
PX-12 has activity as a single agent in models of colorectal, gastric, lung, and pancreatic cancers and hepatomas. Preclinical studies also show that PX-12 enhances the antitumor activity of commonly used anti-cancer agents such as cisplatin, tamoxifen, and Taxol, suggesting that PX-12 may enable the development of more effective combination regimens.
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