PRDX1-IN-2 (compound 15) is a selective inhibitor of the antioxidant enzyme Peroxiredoxin 1 (PRDX1) with an IC50 of 0.35 μM. It reduces mitochondrial membrane potential in SW620 cells, potentially due to increased ROS resulting from PRDX1 inhibition, leading to apoptosis. PRDX1-IN-2 is applicable in colorectal cancer research.

PRDX1-IN-2, at concentrations of 0.5-2 μM for 48 hours, induces a dose-dependent increase in intracellular ROS levels. This compound causes mitochondrial membrane depolarization, reducing mitochondrial membrane potential and ultimately leading to mitochondrial dysfunction. PRDX1-IN-2, administered at 0.5, 1, and 2 μM for 48 hours, induces apoptosis and G2/M cell cycle arrest in colon cancer cells, likely contributing to its antiproliferative effects. Additionally, PRDX1-IN-2, at concentrations ranging from 0.25-2 μM for 48 hours, induces apoptosis in SW620 cells by modulating pro-apoptotic and anti-apoptotic marker proteins related to mitochondrial dysfunction, resulting in an antiproliferative phenotype.

PRDX1-IN-2 (20 mg/kg, ip.; administered once daily for 14 days) demonstrates a higher safety profile compared to the natural product triptolide, likely due to its selective inhibition of PRDX1 activity in C57BL/6J mice. Additionally, PRDX1-IN-2 (2 mg/kg, ig.; administered once daily for 16 days) effectively suppresses tumor growth by inducing apoptosis and is well tolerated in a colorectal cancer cell xenograft model.