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PX 12 is an inhibitor of thioredoxin-1 [1].

Thioredoxin-1 (Trx-1) is a small redox protein with a conserved catalytic site and plays an important role in cells that includes the regulation of trans-activating activity and the DNA binding of redox-sensitive transcription factors [1].

In HT-29 human colon carcinoma cells and MCF-7 human breast cancer, PX 12 prevented the hypoxia-induced increase in HIF-1 protein. Also, PX 12 decreased inducible nitric oxide synthase, HIF-1-trans-activating activity and VEGF formation [2].

In immunodeficient mice bearing HT-29 human colon xenografts, PX 12 decreased the average tumor blood vessel permeability by 63% within 2 hours and returned to pretreatment values after 48 hours. PX 12 reduced tumor-derived VEGF and tumor after 24 hours. Also, Trx-1 showed a rapid decrease within 2 hours and maintained for 24 hours [1]. In mice bearing MCF-7 tumor xenografts, PX 12 reduced HIF-1ɑ and VEGF protein levels [2]. In cancer patients, PX-12 treatment significantly reduced the levels of Trx-1 and VEGF in plasma [3].

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