Rational optimization of a transcription factor activation domain inhibitor
Shaon Basu, Paula Martínez-Cristóbal, Marta Frigolé-Vivas, Mireia Pesarrodona, Michael Lewis, Elzbieta Szulc, C. Adriana Bañuelos, Carolina Sánchez-Zarzalejo, Stasė Bielskutė, Jiaqi Zhu, Karina Pombo-García, Carla Garcia-Cabau, Levente Zodi, Hannes Dockx, Jordann Smak, Harpreet Kaur, Cristina Batlle · 2023
Read Rational optimization of a transcription factor activation domain inhibitor by Shaon Basu, Paula Martínez-Cristóbal, Marta Frigolé-Vivas, Mireia Pesarrodona, Michael Lewis, Elzbieta Szulc, C. Adriana Bañuelos, Carolina Sánchez-Zarzalejo, Stasė Bielskutė, Jiaqi Zhu, Karina Pombo-García, Carla Garcia-Cabau, Levente Zodi, Hannes Dockx, Jordann Smak, Harpreet Kaur, Cristina Batlle (2023) 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-10716049.txt.
Description
Shaon Basu and co-authors improve a drug that blocks a cancer-linked protein switch in a 2023 study. The switch, the androgen receptor's activation domain, helps drive prostate cancer that resists hormone therapy. Such domains are loose and shapeless, long deemed hard to drug, yet their aromatic parts proved key to their work.
The team learned how the domain clumps into droplets when switched on, and what holds those droplets together. Guided by that picture, they reshaped a known weak blocker into tighter versions. The new compounds bound better, shut down the receptor's gene programs, and slowed tumours in cells and in animals. The work hints disordered switches can be designed against.
Catalog record
| CREATOR | Shaon Basu, Paula Martínez-Cristóbal, Marta Frigolé-Vivas, Mireia Pesarrodona, Michael Lewis, Elzbieta Szulc, C. Adriana Bañuelos, Carolina Sánchez-Zarzalejo, Stasė Bielskutė, Jiaqi Zhu, Karina Pombo-García, Carla Garcia-Cabau, Levente Zodi, Hannes Dockx, Jordann Smak, Harpreet Kaur, Cristina Batlle |
|---|---|
| YEAR | 2023 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 126 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |