Evidence map›Paper›PMID 42017803›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Discovery of a Potent Fluorescence Polarization Probe for Identifying USP1 Allosteric Inhibitors.

Jiawei Cheng, Peipei Wang, Pengfei Wang, Jiamin Wang, Baiyang Li, Daqing Fang, Jian He, Xiaobei Hu, Weijuan Kan, Yubo Zhou and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Jiawei ChengKey Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China.
Peipei WangSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Pengfei WangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Jiamin WangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Baiyang LiSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Daqing FangShandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, China.
Jian HeState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Xiaobei HuZhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, China.
Weijuan KanState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Yubo ZhouZhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, China.
Chunpu LiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Jia LiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Hong LiuKey Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, China.ORCID https://orcid.org/0000-0003-3685-6268

Funding

National Key R&D Program of China 2023YFF1205104National Natural Science Foundation of China 22337003National Natural Science Foundation of China 82273766National Natural Science Foundation of China 82574231National Natural Science Foundation of China 92478204Shanghai Institute of Materia Medica, Chinese Academy of Sciences SIMM0120232003Shanghai Institute of Materia Medica, Chinese Academy of Sciences SIMM0320231005Shanghai Institute of Materia Medica, Chinese Academy of Sciences SIMM0420245003Strategic Priority Research Program of the Chinese Academy of Sciences XDA0530102Strategic Priority Research Program of the Chinese Academy of Sciences XDA0580000
6 · The paper itself

Abstract

The deubiquitinating enzyme, ubiquitin-specific protease 1 (USP1), is overexpressed in various tumor types, making it a promising target for cancer therapy. The development of USP1 allosteric inhibitors has progressed rapidly owing to their high selectivity and potency. However, the lack of appropriate chemical tools for developing a binding screen for this site has hampered the discovery of novel ligands. Herein, we developed the first allosteric fluoroprobe and fluorescence polarization (FP) assay for direct validation of USP1 allosteric inhibitors. The FP assay based on allosteric tracer 6-2 enabled the differentiation of known allosteric and catalytic site inhibitors, providing a robust and scalable tool for high-throughput screening. In addition, a novel class of potent tetrahydroisoquinoline USP1 inhibitors was identified, and the representative compound 14a possessed superior enzymatic and cellular activity compared with the clinical candidate KSQ-4279, with potent in vivo anti-DLBCL efficacy and good druggability. Collectively, this study provides a valuable fluoroprobe, FP assay platform, and lead compounds targeting USP1 for further structural optimization and antitumor mechanism studies.

Indexed as

Enzyme InhibitorsFluorescence PolarizationFluorescent DyesUbiquitin-Specific ProteasesAllosteric RegulationAnimalsCell Line, TumorHigh-Throughput Screening AssaysHumansEnzyme InhibitorsFluorescent DyesUbiquitin-Specific ProteasesUSP1 protein, humanAllosteric inhibitorAnti‐lymphomaFP‐based assayTHIQ skeletonUSP1

Identifiers

PMID42017803
PMCPMC13335693

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.