Maya R. MacLean, Bianca Laura Bernardoni, Wasundara Fernando, Giovanni Petrarolo, Ilaria D’Agostino, Cheryl A. Dean, Jaganathan Venkatesh, Christopher S. Hughes, Kerry B. Goralski, Geetha Subramanian, Raj Pranap Arun, Hannah F. Cahill, Olivia L. Walker, Lynn N. Thomas, Robert C. Douglas, Concettina La Motta, Paola Marcato
, significantly reduces only ALDH1A3-dependent tumor growth and lung metastasis in TNBC xenografts. These effects are accompanied by selective inhibition of ALDH1A3 target genes in tumors, while pharmacokinetic studies demonstrate broad tissue distribution to metastatic sites, sustained target engagement, and favorable oral bioavailability. CLM296 shows no observable toxicity in preclinical models, supporting its potential as a first-in-class ALDH1A3 inhibitor for ALDH1A3-positive cancers.