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Research team led by Vortex Therapeutics founders Drs. Sarki Abdulakdir and Gary Schiltz publish new work that describes the anti-tumor efficacy and mechanism of action of their first-in-class MYC inhibitors.

A research team at Northwestern University, led by Vortex Therapeutics founders Dr. Sarki Abdulkadir and Dr. Gary Schiltz, has published new work defining the precise epigenetic and transcriptional mechanism of action of their small-molecule MYC inhibitor, MYCi975.

The study, published in Science Advances (PMID: 35476451), provides a high-resolution map of how MYCi975 selectively alters the genetic landscape of cancer cells, providing a clear rationale for future combination treatments.

The key findings demonstrate that MYCi975:

  • Selectively Modulates Gene Expression: The inhibitor does not cause a global shutdown, but rather selectively alters the MYC and MAX cistromes, prioritizing the downregulation of genes critical for cell cycle and signaling while sparing genes related to core cellular processes.
  • Alters Epigenomic Landscape: MYCi975 suppresses MYC-regulated lineage factors by altering chromatin accessibility and acetylation which are mechanisms that tumors use to maintain their identity and drive growth.
  • Creates Synergistic Vulnerabilities: By suppressing these lineage factors, MYCi975 sensitized resistant prostate cancer cells to Enzalutamide and other standards of care.

“Understanding the precise epigenetic changes caused by our MYC inhibitor allows us to move away from trial-and-error and toward a truly rational combination therapy design,” said Dr. Sarki Abdulkadir, Principal Investigator and Vortex co-founder. “This work is critical because it explains why our inhibitor is well-tolerated and how it can be paired with existing standard-of-care drugs to overcome acquired drug resistance in aggressive cancers.”

The findings reinforce the unique, first-in-class nature of Vortex Therapeutics’ small-molecule platform and accelerates its strategy for clinical development as a backbone for combination cancer regimens.