3-Methyltoxoflavin (3-methyl toxoflavin) is an effective inhibitor of protein disulfide isomerase (PDI) and its IC50 value is 170 nM.

PDI:170 nM

3-Methyltoxoflavin is an effective inhibitor of Protein disulfide isomerase (PDI), exhibiting significant potency with an IC50 value of 170 nM, and demonstrating marked toxicity across various human glioblastoma cell lines. It stands out as the most potent PDI inhibitor identified in screening efforts. Research involving Bromouridine labeling and sequencing (Bru-seq) has shown that 3-Methyltoxoflavin activates the Nrf2 antioxidant response, triggers ER stress response, and promotes autophagy. It achieves this by increasing the transcription and protein levels of heme oxygenase 1 and SLC7A11, while simultaneously downregulating expression of PDI target genes, such as TXNIP and EGR1. Notably, the cell death induced by 3-Methyltoxoflavin does not occur through traditional pathways like apoptosis or necrosis, but rather through a combination of autophagy and ferroptosis.