Authors
Matthew W Boudreau, Vitor F Freire, Sophie C Corbett, Lucero Martínez-Fructuoso, Shilpa R Shenoy, Wenyu Yu, Rohitesh Kumar, Christopher C Thornburg, Rhone K Akee, Brian D Peyser, Qinqin Jiang, Jennifer Splaine, Jamie L Pfaff, Dongli Yu, Benjamin C Chandler, Dinah M Abeja, Katherine A Donovan, Jianwei Che, Benjamin L Lampson, Mariana Cooke, Marcelo G Kazanietz, Patricia Szajner, Jennifer A Smith, Vidyasagar Koduri, Tanja Grkovic, Barry R O'Keefe, William G Kaelin
Published in
Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 39. Pages e2625189123. Sep 29, 2026. Epub Sep 25, 2026.
Abstract
Many genetically validated targets in cancer, including the transcription factor β-catenin (β-cat), have historically been viewed as undruggable. Cell-based phenotypic screening of chemical compounds can reveal unanticipated biological and pharmacological principles. Natural products are powerful probes because of their superior structural diversity, drug-like properties, and biological activities as compared to unoptimized synthetic compounds. We screened 326,304 natural product mixtures (40,744 extracts and 285,560 fractions derived from them) using mammalian cells expressing an oncogenic version of β-cat fused to a suicide protein. Multiple fractions degraded the β-cat fusion protein or drove it into a compartment where both fusion partners were apparently inactive. The active natural product from one of the latter specifically activates novel, but not classical, protein kinase Cs and thereby relocates β-cat to juxtamembrane vacuolar structures. These findings suggest a path for inactivating oncogenic β-cat and underscore the power of screening natural product collections with robust phenotypic assays.
PMID:
42789292
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 21
- Comments 0