Discovery and Preclinical Evaluations of Potent, Selective, and Allosteric Covalent WRN Inhibitors with Improved PK Properties.
1/5 보강
PICO 자동 추출 (휴리스틱, conf 2/4)
유사 논문P · Population 대상 환자/모집단
추출되지 않음
I · Intervention 중재 / 시술
significant interest due to its implication as a synthetic lethal target in microsatellite instability-high (MSI-H) cancers
C · Comparison 대조 / 비교
추출되지 않음
O · Outcome 결과 / 결론
It also demonstrated favorable preclinical pharmacokinetic properties with superior plasma stability and exposure compared with VVD-214. Furthermore, compound showed statistically significant antitumor activity in the HCT116 xenograft mouse model with clear dose dependence.
Werner syndrome helicase (WRN) has received significant interest due to its implication as a synthetic lethal target in microsatellite instability-high (MSI-H) cancers.
APA
Xu Z, Xiao Q, et al. (2026). Discovery and Preclinical Evaluations of Potent, Selective, and Allosteric Covalent WRN Inhibitors with Improved PK Properties.. ACS medicinal chemistry letters, 17(2), 554-560. https://doi.org/10.1021/acsmedchemlett.5c00787
MLA
Xu Z, et al.. "Discovery and Preclinical Evaluations of Potent, Selective, and Allosteric Covalent WRN Inhibitors with Improved PK Properties.." ACS medicinal chemistry letters, vol. 17, no. 2, 2026, pp. 554-560.
PMID
41704373
Abstract
Werner syndrome helicase (WRN) has received significant interest due to its implication as a synthetic lethal target in microsatellite instability-high (MSI-H) cancers. Here we report the discovery of a novel allosteric covalent WRN inhibitor, compound , via structure-based medicinal design and pharmacokinetic optimization from VVD-214. Compound occupied a new cavity and formed an additional hydrogen bond with K894, thereby improving its activities. Compound exhibited high antiproliferation inhibitory activity against HCT116, an MSI-H colorectal cancer cell line. It also demonstrated favorable preclinical pharmacokinetic properties with superior plasma stability and exposure compared with VVD-214. Furthermore, compound showed statistically significant antitumor activity in the HCT116 xenograft mouse model with clear dose dependence.
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