A Type II CDK6 Degrader Enables Cellular Targeting beyond the Limits of Type II Inhibition
Ji Hyeon Kim, Caitlin E. Mills, Zuzanna Kozicka, Daniel C. Scott, Cyrus Jin, Zixuan Jiang, Brendan G. Dwyer, Qixiang Geng, Sean T. Toenjes, Woong Sub Byun, Dina ElHarouni, Hongyu Li, Keith L. Ligon, Abby M. Thornhill, Hannah M. Jones, Bryan A. Romero, Stephen M. Hinshaw, Benjamin L. Ebert, Brenda A. Schulman, Katherine A. Donovan, Eric S. Fischer, Nathanael S. Gray · 2026
Read A Type II CDK6 Degrader Enables Cellular Targeting beyond the Limits of Type II Inhibition by Ji Hyeon Kim, Caitlin E. Mills, Zuzanna Kozicka, Daniel C. Scott, Cyrus Jin, Zixuan Jiang, Brendan G. Dwyer, Qixiang Geng, Sean T. Toenjes, Woong Sub Byun, Dina ElHarouni, Hongyu Li, Keith L. Ligon, Abby M. Thornhill, Hannah M. Jones, Bryan A. Romero, Stephen M. Hinshaw, Benjamin L. Ebert, Brenda A. Schulman, Katherine A. Donovan, Eric S. Fischer, Nathanael S. Gray (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/PMC13352627.txt.
Description
Ji Hyeon Kim leads a 2026 drug study that turns a weak kinase blocker scaffold into a targeted protein degrader for CDK6. Breaker drugs built from blockers usually keep blocking action, and type II CDK blockers are notoriously weak in cells. Starting from regorafenib, the team built a small library of bifunctional molecules that recruit the CRL4-CRBN disposal machinery.
Protein-wide mass checks unexpectedly flagged CDK5 and CDK6 as disposal targets, though the parent drug does not block them. Tuning gave JHK-02-108-2, a selective CDK6 degrader with no hook effect at high doses. It destroys CDK6 strongly despite weak binding and almost no blocking, showing degradation can reach targets that inhibition alone cannot.
Catalog record
| CREATOR | Ji Hyeon Kim, Caitlin E. Mills, Zuzanna Kozicka, Daniel C. Scott, Cyrus Jin, Zixuan Jiang, Brendan G. Dwyer, Qixiang Geng, Sean T. Toenjes, Woong Sub Byun, Dina ElHarouni, Hongyu Li, Keith L. Ligon, Abby M. Thornhill, Hannah M. Jones, Bryan A. Romero, Stephen M. Hinshaw, Benjamin L. Ebert, Brenda A. Schulman, Katherine A. Donovan, Eric S. Fischer, Nathanael S. Gray |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 37544 |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |