IACS-16559 / UT MD Anderson Cancer Center - LARVOL DELTA

Low physiological pH drives P300 mediated acetylation of PARP1 and promotes PARP inhibitor resistance (AACR 2026) - "In multiple in vivo patient-derived and syngeneic EOC models, novel p300 bromodomain inhibitors, TT125-802 and IACS-16559, synergize with PARP inhibitors (olaparib or saruparib) to inhibit the growth of therapy-resistant tumors. Together, our findings establish p300 as a promising therapeutic target for overcoming acidosis-driven PARPi resistance."

Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

Preclinical development and characterization of IACS-16559, a dual bromodomain inhibitor of CBP/EP300, and its potential in AML subtypes (AACR 2025) - "Clinical validation of bromodomain inhibition of paralogs CBP and EP300 is undergoing in multiple clinical trials, including both hematological diseases and solid tumors, using EP31670, CCS1477 and TT125-802, while selective CBP or EP300 inhibition is being explored preclinically. However, in contrast, long-term treatment in the MLL-AF9 (MOLM14) model resulted in antagonistic effects. These findings underscore the complexities of combinatorial therapeutic development and emphasize the critical need for careful selection of robust therapeutic combinations and consideration of the genetic background in the target disease."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BRD4 • EP300