OXPHOS Inhibitors

Phenformin is a potent biguanic OXPHOS complex I inhibitor that has shown greater than 30% tumor growth inhibition in 5 out of 12 pancreatic adenocarcinoma xenograft models (Rajeshkumar et al. 2017). It is more potent than metformin, another OXPHOS complex I inhibitor, which only suppressed tumor growth via mitochondrial membrane inhibition to the same degree in 3 out of 12 pancreatic adenocarcinoma xenograft models with a five-fold higher dose (Rajeshkumar et al. 2017). Additionally, phenformin does not require a cellular transporter, unlike metformin (Iversen et al. 2017). OXPHOS inhibitors, such as phenformin, have also been shown to resensitize previously therapy-resistant cancer cells (Matassa et al. 2016). Due to its high efficacy, the Pancreass Kickers plan to incorporate phenformin into their treatment in conjunction with a Krebs cycle inhibitor, devimistat (CPI-613).