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Peer-Reviewed Publication
Proc Natl Acad Sci U S A2026;123(33):e2529603123.August 18, 2026Journal Article

Cryptic small-molecule binding sites in the ARID1B DNA-binding domain.

Christine E Carbone1, Heike Schönherr1, Victor Y Zhao1, Levi Pierce1, Jing He1, Kelley C Shortsleeves1, Sandor Babik1, Philip A Venter1, Elaine B Krueger1, Pascal D Fortin1, Jeremy D Wilbur1, Michael J Holliday1
1Relay Therapeutics Inc., Cambridge, MA 02139.
PubMed DOI

Abstract

Genetic depletion of ARID1B has been shown to act in a synthetically lethal manner to selectively kill cancer cells with mutations in the tumor suppressor ARID1A, one of the most frequently altered proteins in human cancer. However, no precision therapeutic targeting ARID1B in ARID1A-mutant cancer has been developed due to the lack of a classically druggable small-molecule binding pocket on ARID1B…

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