Discovery of a paralog-selective p300 protein degrader with potent anti-cancer activity in hematological malignancies
Marwa S. Asem, Yan Zhai, Xiaohong Song, Milad Rouhimoghadam, Sreenivas Punna, Fritz G. Buchanan, Daniel T. Cohen, Ryan McClure, Stephanie Sandoval, Anlu Chen, Shaun McLoughlin, Colin Woodford, Peter Kovar, Vlasios Manaves, Alla V. Korepanova, Justin M. Reitsma, Andrea Shergalis, Judith A. Ronau, Yif · 2026
Read Discovery of a paralog-selective p300 protein degrader with potent anti-cancer activity in hematological malignancies by Marwa S. Asem, Yan Zhai, Xiaohong Song, Milad Rouhimoghadam, Sreenivas Punna, Fritz G. Buchanan, Daniel T. Cohen, Ryan McClure, Stephanie Sandoval, Anlu Chen, Shaun McLoughlin, Colin Woodford, Peter Kovar, Vlasios Manaves, Alla V. Korepanova, Justin M. Reitsma, Andrea Shergalis, Judith A. Ronau, Yif (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13358106.txt.
Description
Marwa Asem and co-authors report a drug-like compound that destroys one cancer-linked protein while sparing its near twin. The protein, p300, helps switch on genes that blood cancers depend on. Its twin, CBP, is so similar that past blockers hit both and caused dose-limiting harm. A degrader takes a different route: it tags the target for the cell's disposal machinery instead of just blocking it.
Their compound forms a steadier three-part complex with p300 than with the twin, which drives stronger tagging. The tag lands on a lysine spot found only on p300, a new route to selectivity the team uncovered. Blood cancers such as myeloma, lymphoma, and acute myeloid leukemia proved very sensitive, and tumors in mice shrank. The work, published in 2026, sets out selective p300 removal as a distinct treatment strategy.
Catalog record
| CREATOR | Marwa S. Asem, Yan Zhai, Xiaohong Song, Milad Rouhimoghadam, Sreenivas Punna, Fritz G. Buchanan, Daniel T. Cohen, Ryan McClure, Stephanie Sandoval, Anlu Chen, Shaun McLoughlin, Colin Woodford, Peter Kovar, Vlasios Manaves, Alla V. Korepanova, Justin M. Reitsma, Andrea Shergalis, Judith A. Ronau, Yif |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 76 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |