Huge congrats to first author @cestieger.bsky.social for leading this effort!
Thanks to @novartis.bsky.social and @themarkfdn.bsky.social for their support.
#MolecularTherapeuticsInitiative #BerkeleyChemistry #BerkeleyMCB

This establishes a new therapeutic modality - using small-molecule-induced proximity for targeted epigenetic reprogramming - to silence transcriptional networks long considered out of reach.
A potential blueprint for pharmacologically “turning off” disease-driving transcription factors.

In androgen-independent prostate cancers expressing both AR and the “undruggable” truncation variant AR-V7, where AR antagonists inhibit only ~40% of AR activity...
Our AR/AR-V7 TRACER, which links an AR SARM to an MBD2 recruiter, suppresses more than 90% of AR transcriptional activity.

TRACERs enable epigenetic silencing of transcription factors through fully small-molecule control.
We demonstrate that TRACERs can potently and selectively repress the transcriptional programs of estrogen receptor (ER) and androgen receptor (AR/AR-V7).

Haha I would never…

- Mutations mimicking glues by @brianliau.bsky.social al and Ning Zheng
- Covalent and bivalent glue engagement by @dannomura.bsky.social, Nathanael Gray, @georgwinter.bsky.social and @alessiociulli.bsky.social
- And finish it of with a discussion on general mode-of-action.

Thanks to @olzmannlab.bsky.social for the great collaboration, and also thanks to @novartis.bsky.social @themarkfdn.bsky.social