Evidence map›Paper›PMID 34841869›Full record

ArticleJournal of medicinal chemistry2022

Identification of Small Molecule Inhibitors of RNase L by Fragment-Based Drug Discovery.

Jinle Tang, Beihua Dong, Ming Liu, Shuyan Liu, Xiaogang Niu, Christina Gaughan, Abhishek Asthana, Huan Zhou, Zhengshuang Xu, Guoliang Zhang and 2 more

Open access · greenAbstract read
In one paragraph

Article in Journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.6field-weighted citation impact, top 36% of its field
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

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
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  3. The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025
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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

12 authors at 4 institutions in 2 countries.

Jinle TangState Key Laboratory of Chemical Oncogenomics, Laboratory of Structural Biology and Drug Discovery, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.ORCID 0000-0002-1844-6516
Beihua DongDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, United States.
Ming LiuState Key Laboratory of Chemical Oncogenomics, Laboratory of Structural Biology and Drug Discovery, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Shuyan LiuNational Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen 518112, China.
Xiaogang NiuCollege of Chemistry and Molecular Engineering, Beijing Nuclear Magnetic Resonance Center, Peking University, Beijing 100871, China.
Christina GaughanDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, United States.
Abhishek AsthanaDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, United States.ORCID 0000-0002-5429-6199
Huan ZhouShanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.
Zhengshuang XuState Key Laboratory of Chemical Oncogenomics, Laboratory of Structural Biology and Drug Discovery, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Guoliang ZhangNational Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen 518112, China.
Robert H SilvermanDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, United States.
Hao HuangState Key Laboratory of Chemical Oncogenomics, Laboratory of Structural Biology and Drug Discovery, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Peking University · CNCleveland Clinic Lerner College of Medicine · USSouthern University of Science and Technology · CNChinese Academy of Sciences · CN

Funding

ANTIVIRAL MECHANISMS OF 2-5A-DEPENDENT RNASE LR01AI135922 · NIAID · CLEVELAND CLINIC LERNER COM-CWRU · PI SILVERMAN, ROBERT H. · 2017 to 2021
$2.0M
NIAID NIH HHS R01 AI135922
6 · The paper itself

Abstract

The pseudokinase-endoribonuclease RNase L plays important roles in antiviral innate immunity and is also implicated in many other cellular activities. The inhibition of RNase L showed therapeutic potential for Aicardi-Goutières syndrome (AGS). Thus, RNase L is a promising drug target. In this study, using an enzyme assay and NMR screening, we discovered 13 inhibitory fragments against RNase L. Cocrystal structures of RNase L separately complexed with two different fragments were determined in which both fragments bound to the ATP-binding pocket of the pseudokinase domain. Myricetin, vitexin, and hyperoside, three natural products sharing similar scaffolds with the fragment AC40357, demonstrated a potent inhibitory activity

Indexed as

Drug DiscoveryBiological ProductsEndoribonucleasesHigh-Throughput Screening AssaysHumansSmall Molecule Libraries2-5A-dependent ribonucleaseBiological ProductsEndoribonucleasesSmall Molecule Libraries

Identifiers

PMID34841869
PMCPMC10620946
OpenAlexW3215198071

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.