Discovery of RP-37 analogues as potent, selective irreversible inhibitors targeting DNA polymerase theta (POLθ)

RSC Medicinal Chemistry 2026 Open access

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Authors: Zhenwei Wang, Mengyuan Qiu, Deming Liu, Yanzhen Yu, Dongyan Gu, Fengmin Zhang, Rong Sheng
DOI: 10.1039/d5md00830a
Cited by: 1
References: 23

Abstract

Enzymatic IC 50 = 1.54 nM (POLθ polymerase domain). Cellular IC 50 = 1.16 μM (DLD-1 BRCA2 −/− ; ∼5-fold enhancement). Sustained target engagement via irreversible inhibition.

Fields of Study & Subjects

DNA Repair Mechanisms Microtubule and mitosis dynamics PARP inhibition in cancer therapy

Publication details

Journal / source
RSC Medicinal Chemistry
Publisher
Royal Society of Chemistry (RSC)
Volume
17
Issue
3
Pages
1694–1708
Publication date
1 January 2026
Language
EN