Abstract 6987: MYC condensate-modulating small molecules demonstrate robust antitumor activity in animal models of ovarian cancer and other solid tumors

Abstract The transcription factor MYC is a critical driver of cancer, implicated in 70% of malignancies and amplified in approximately 30% of ovarian cancers, where it contributes to aggressive tumor progression. Despite its pivotal role in oncogenesis, MYC has eluded traditional structure-based drug discovery efforts due to the absence of well-defined drug binding sites and its dependence on highly dynamic interactions. Here, we are deploying condensate biology and phenotypic screening to identify and optimize small molecule condensate modulators (c-mods) to modify MYC oncogenic function. In vitro, MYC c-mods dissolve MYC nuclear condensates, selectively repress MYC-driven gene expression, and induce cell killing in a spectrum of ovarian cancer and esophageal cancer cell lines. Advanced MYC c-mods optimized using Dewpoint’s AI/ML-powered end-to-end platform are orally bioavailable and yield tumor stasis and regression in in vivo models of ovarian cancer at tolerated daily doses. We demonstrate that the antitumor activity of the MYC c-mods extends to additional in vivo models from multiple indications and correlates with repressed MYC activity in tumors. Citation Format: Ann Boija, Bede Portz, Yingda Ye, Jian-Guo Ren, Thomas Durand-Reville, Kip West, Isaac Klein. MYC condensate-modulating small molecules demonstrate robust antitumor activity in animal models of ovarian cancer and other solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6987.