PX-12

PX-12 is an orally bioavailable small molecule and the first thioredoxin-1 (Trx-1) inhibitor to undergo clinical development. It irreversibly binds to Trx-1, primarily through thioalkylation of the Cys73 residue, inhibiting its redox activity. This inhibition disrupts DNA synthesis and the regulation of transcription factors involved in cell proliferation and survival, leading to growth inhibition and induction of apoptosis in cancer cells[1][2][3][5]. PX-12 also downregulates hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF), contributing to its anti-tumor effects[2][7]. Preclinical studies have shown that PX-12 reduces tumor microvascular permeability, inhibits tubulin polymerization via cysteine oxidation, and demonstrates antitumor activity in various models including colon cancer xenografts[5][8]. It has been investigated as a potential treatment for advanced metastatic cancers such as colorectal, gastric, lung, gastrointestinal malignancies, often in combination with chemotherapy[2][5].

Other names

1-methylpropyl 2-imidazolyl disulfide