PRT3789 Is a First-in-Human SMARCA2-Selective Degrader That Induces Synthetic Lethality in <i>SMARCA4</i> -Mutated Cancers
PRT3789 selectively degrades SMARCA2 and demonstrates activity in SMARCA4-deficient cancers while sparing wild-type models, validating paralog synthetic lethality, and supporting clinical development in SMARCA4-mutated patients, a population with high unmet need.
Authors
- Alice Da Silva
- Chaofeng Dai
- Joseph Rager (ORCID: https://orcid.org/0009-0004-6008-9630)
- Sandy Geeganage
- Liang Lu
- Chris Tankersley
- Jennifer Xavier (ORCID: https://orcid.org/0000-0003-4173-8784)
- Ganfeng Cao (ORCID: https://orcid.org/0000-0003-3468-2057)
- Monisha Sivakumar (ORCID: https://orcid.org/0009-0002-8937-4289)
- Peggy Scherle (ORCID: https://orcid.org/0000-0003-0783-6815)
- Carly Bachner
- Andrew P. Combs (ORCID: https://orcid.org/0000-0003-1418-5168)
- Koichi Ito (ORCID: https://orcid.org/0000-0003-1421-3122)
- Jessica Burtell (ORCID: https://orcid.org/0000-0002-7763-6379)
- Klare Bersch
- Miles Cowart
- Anjana Agarwal (ORCID: https://orcid.org/0009-0008-7625-1240)
- Bruce Ruggeri (ORCID: https://orcid.org/0009-0002-0095-873X)
- Kris Vaddi (ORCID: https://orcid.org/0009-0009-8581-6511)
- Stefan Ruepp
- Komali Vykuntam
- Jack Carter (ORCID: https://orcid.org/0000-0002-7784-7897)
- Neha Bhagwat (ORCID: https://orcid.org/0009-0002-5766-0272)
- William Novotny
- Hsin‐Yao Tang (ORCID: https://orcid.org/0000-0003-1838-018X)
- Min Wang (ORCID: https://orcid.org/0009-0004-9364-1284)
- Olusola Peace Osinubi
- Jane Huang
- Alexander Grego
- Catline Nobre
- Philip Pitis
- Ludovic Bigot (ORCID: https://orcid.org/0009-0009-0820-5370)
- Hong Lin (ORCID: https://orcid.org/0000-0002-7493-5963)
- Andrew Moore
- Joy M. Cote (ORCID: https://orcid.org/0000-0002-2570-267X)
- Arpita Mondal
- Chaoyi Xu (ORCID: https://orcid.org/0000-0002-9870-4297)
- Michael Hulse
- Anthony Reichelderfer
- Diane Heiser (ORCID: https://orcid.org/0009-0008-1757-914X)
- CoreyHannah Basch
- Sang Hyun Lee
- Justin Kurian
- Manoel C.P. Soares
- J. Park
- Bo Shen
- Tom Emm
- Melissandre Meteau
Institutions
- The Wistar Institute (US)
- Inserm (FR)
- Wilmington University (US)
- Université Paris-Saclay (FR)
- Institut Gustave Roussy (FR)
- PreludeDx (United States) (US)
Publication Details
- Journal
- Cancer Research
- Published
- 2025-09-24
- DOI
- https://doi.org/10.1158/0008-5472.can-25-1141
- Citations
- 5
- Primary Topic
- Chromatin Remodeling and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 4.03