Association details:
Biomarker:IGH translocation
Cancer:Acute Myelogenous Leukemia
Drug:GT19077 (MYC inhibitor)
Evidence Level:
Sensitive: D – Preclinical

1547 Discovery of GT19077, a c-Myc/Max Protein-Protein Interaction (PPI) Small Molecule Inhibitor, for Targeting c-Myc-Driven Blood Cancers

Published date:
Dysregulated c-Myc is one of major oncogene drivers in B-cell lymphoma, MM and AML. Therefore, GT19077 was evaluated in a panel of 14 hematologic malignant cell lines expressing dysregulated c-Myc or other oncogene drivers. The results showed that GT19077 selectively inhibited the proliferation of all seven B-cell malignant cell lines tested, carrying IGH/Myc translocations (6/7) or Kras G12A mutation (1/7), with IC50s as low as 160 nM. In addition, two myeloblast cell lines and one monoblast cell line were also sensitive to GT19077 with IC50 of 300-700 nM. . Importantly, GT19077 effectively inhibits the proliferation of B-cell lymphoma, MM and AML cells carrying c-Myc genetic alterations, including IGH/Myc translocations, but lacks activity in blood cancer cells expressing other oncogene drivers.