Mitophilix

Mitophilix, Inc. developed a series of potent, orally active OXPHOS Complex I (NDFUS7 subunit) inhibitors with nanomolar potency and favorable safety profiles. These compounds significantly inhibited the growth of PDAC cell lines and were confirmed to directly target NDUFS7 through resistance profiling and sequencing. Multi-omics analyses showed downregulation of DNA repair genes, and the inhibitors demonstrated strong synergy with chemotherapy and FDA-approved drugs. We believe that our work represents a significant advancement and addresses several critical issues in cancer treatment. Here are the key points highlighting the significance: 1. Novel Mechanism of Action: Unlike conventional cancer therapies that primarily target cell division or DNA synthesis, NDUFS7 inhibitors specifically target the OXPHOS pathway. 2. Overcoming Drug Resistance: NDUFS7 inhibitors can overcome resistance by targeting a different and essential metabolic pathway. 3. Cancer Stem Cells: CSCs are resistant to conventional therapies and are responsible for tumor recurrence and metastasis. NDUFS7 inhibitors can target CSCs, potentially reducing relapse rates and improving long-term survival outcomes. 4. Broad Therapeutic Potential: Beyond PDAC, the reliance on OXPHOS is evident in other cancers, including colorectal cancer, non-small cell lung carcinoma (NSCLC), and certain leukemias. 5. Combination Therapy: NDUFS7 inhibitors have shown significant synergy with standard-of-care chemotherapies and ROCK1/2 inhibitors. 6. Robust Preclinical Data: Our extensive preclinical studies have validated the efficacy and safety of NDUFS7 inhibitors. Our inhibitors delay tumor growth, reduce cancer cell proliferation, and exhibit acceptable toxicity profiles. Should you be interested in engaging with us, please contact Ruslan Pryadun at ruslan.pryadun@mitophilix.com