Zolucatetide, A Modified Peptide Polymacrocycle from Parabilis is the First β-catenin/TCF4 PPI Inhibitor to Reach the Clinic | drughunters.com/4gsz87A Brian White of Parabilis Medicines presented the discovery story of zolucatetide (FOG-001), a β-catenin/TCF4 interaction inhibitor currently in a Ph. 1/2 trial for advanced solid tumors, at the ACS Fall 2025 meeting. The starting point for this stapled peptide was discovered using the company’s Helicon™ platform for identifying hyperstabilized α-helical peptides (stay tuned for Drug Hunter’s upcoming modality brief on stapled peptides). Zolucatetide incorporates multiple backbone cyclizations to enforce helicity, limit solvent-exposed amide hydrogen atoms, and enable cytosolic exposure. This case study will examine the challenges and opportunities that exist in modulating the Wnt/β-catenin pathway and how Parabilis employed their platform to generate the hit compound that led to the first selective inhibitor of the β-catenin/CFT4 PPI to enter human trials. Read it on Drug Hunter: drughunters.com/4gsz87A