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A First in Class Small Molecule as a Novel YB1 Inhibitor
Oregon Health and Science University
Small molecule
Oncology
Hit To Lead or Lead Optimization
• An azopodophyllotoxin small molecule, SU056, that potently inhibits tumor growth and progression via YB-1 inhibition. This YB-1 inhibitor inhibits cell proliferation, resistance to apoptosis in ovarian cancer (OC) cells, and arrests in the G1 phase.
• The development of resistance to chemotherapy treatment in solid tumors is associated with up-regulation of the DNA/RNA binding protein Y box binding protein 1 (YB-1) and a worsened prognosis for cancer patients. Inventors have developed a first-in-class small molecule inhibitor of YB-1 that synergizes with chemotherapy to reduce ovarian cancer progression and potentially patient mortality.
• Ovarian cancer has a high mortality rate, with frequent development of treatment resistance and disease relapse. YB-1 has a wellestablished role in cancer, increasing the stability of many oncogenic transcripts which are associated with disease progression and treatment resistance, and elevated YB-1 expression is associated with shorter term survival in ovarian cancer patients.
• Inventors have developed a novel inhibitor of YB-1 with validated efficacy in ovarian cancer models and the potential to improve outcomes in a broad range of cancers that demonstrate treatment resistance.
WO2022120242A1
Y box binding protein 1 inhibition as a targeted therapy for ovarian cancer. Cell Chem Biol (2021)
