Vortex Therapeutics founders Drs. Sarki Abdulkadir and Gary Schiltz publish groundbreaking research on the identification and characterization of the first orally bioavailable small molecule MYC inhibitor.

Vortex Therapeutics today celebrated the publication of groundbreaking research by its founders, Dr. Sarki Abdulkadir and Dr. Gary Schiltz of Northwestern University, detailing the identification and characterization of their lead therapeutic candidate, a first-in-class, orally bioavailable small molecule MYC inhibitor.

The study, titled “Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy,” was published in the journal Cancer Cell (PMID: 31679823) and addresses one of oncology’s most formidable challenges: directly targeting the MYC oncogene, which drives growth in an estimated 70% of human cancers.

The published work centers on the initial lead compound, MYCi361, and an improved analog, MYCi975, which exhibits superior tolerability. The research confirms that these compounds:

• Directly Engage MYC: The small molecules enter cancer cells, disrupting the critical MYC/MAX dimerization required for MYC’s cancer-promoting function.
• Induce Degradation: They enhance the phosphorylation of MYC, leading to its proteasome-mediated degradation, effectively eliminating the tumor driver.
• Demonstrate Bioavailability: The study showed that the inhibitors are well tolerated in vivo, setting the stage for developing a patient-friendly, orally administered drug.

Furthermore, the research demonstrated a powerful synergistic effect: MYCi361 was shown to increase tumor immune cell infiltration and sensitize tumors to anti-PD1 immunotherapy in mouse models.

“This publication is a true landmark, demonstrating that MYC is a druggable target and providing a clear path to an oral therapy,” said Dr. Sarki Abdulkadir, Principal Investigator and Founder. “Successfully developing a potent, orally bioavailable inhibitor that also enhances the immune response has the potential to redefine treatment for numerous aggressive, resistant cancers.”

“The successful design of an orally bioavailable molecule that can hit a challenging target like MYC is a testament to a highly integrated and robust collaboration between medicinal chemists and biologists. We’ve optimized the compound’s properties to make it a viable clinical candidate” added Dr. Gary Schiltz, Vortex co-founder.

The findings lay the crucial foundation for Vortex Therapeutics as it accelerates the preclinical development of MYCi975 toward clinical trials.