AP-3-84 / The Wistar Institute - LARVOL DELTA

Disruption of the Retinoblastoma Lxcxe Region Induces Cell Death in AML By Activation of the Unfolded Protein Response Leading to NOXA Induction (ASH 2024) - "We also observed an increase in cardiolipin levels consistent with lipid peroxidation changes after AP-3-84 treatment, supporting the contribution of mitochondria to activation of cell death pathways.We conclude that AP-3-84 triggers cell death in AML by activating the UPR via PERK-eIF2a-ATF4-NOXA pathway involving mitochondrial regulation. Our results indicate that Rb1 LxCxE domain may represent a novel therapy target in AML."

Acute Myelogenous Leukemia • Eye Cancer • Hematological Malignancies • Leukemia • Retinal Disorders • Retinoblastoma • Solid Tumor • Targeted Protein Degradation • ATF3 • ATF4 • DDIT3 • EIF2A • EIF2S1 • GLI2 • RB1

Targeting retinoblastoma protein in tumor-associated macrophages suppresses ovarian cancer progression (AACR 2024) - "Using ovalbumin-overexpressing ovarian cancer cell line, we documented the accumulation of antigen-specific T cells in the TME associated with a substantial delay of ovarian cancer upon AP-3-84 therapeutic Rb targeting.Ex vivo, we observed an analogous cell death induction by AP-3-84 treatment in TAMs from post-surgery ascites from ovarian cancer patients. Using available datasets, we further documented that an increase in Rb expression in the TME myeloid cells is associated with poorer prognosis.Overall, our data supports that therapeutic targeting of the Rb LxCxE motif is a promising approach for ovarian cancer treatment due to depletion of TAMs and re-shaping the ovarian cancer TME."

IO biomarker • Eye Cancer • Oncology • Ovarian Cancer • Retinoblastoma • Solid Tumor • CD8 • RB1

Targeting acute myeloid leukemia cell death via small molecule AP-3-84 binding to the LxCxE pocket of Rb1 (AACR 2023) - "We identify a new small molecule, AP-3-84, with therapeutic potential in AML by its binding to the LxCxE pocket of Rb1 triggering mitochondria-mediated cell apoptosis."

Acute Myelogenous Leukemia • Eye Cancer • Hematological Malignancies • Leukemia • Oncology • Retinoblastoma • Solid Tumor • ANXA5 • ATF3 • ATF4 • CASP3 • GLI2 • RB1