Evidence map›Paper›PMID 36449366›Full record

ArticleJournal of medicinal chemistry2022

Transcriptional Inhibition of MicroRNA miR-122 by Small Molecules Reduces Hepatitis C Virus Replication in Liver Cells.

Cole Emanuelson, Nicholas Ankenbruck, Rohan Kumbhare, Meryl Thomas, Colleen Connelly, Yasmine Baktash, Glenn Randall, Alexander Deiters

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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 35% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
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

8 authors at 3 institutions in 1 country.

Cole EmanuelsonDepartment of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Nicholas AnkenbruckDepartment of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Rohan KumbhareDepartment of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Meryl ThomasDepartment of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Colleen ConnellyDepartment of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.
Yasmine BaktashDepartment of Microbiology, The University of Chicago, Chicago, Illinois 60637, United States.
Glenn RandallDepartment of Microbiology, The University of Chicago, Chicago, Illinois 60637, United States.
Alexander DeitersDepartment of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.ORCID 0000-0003-0234-9209
University of Pittsburgh · USUniversity of Chicago · USNorth Carolina State University · US

Funding

Hepatitis C Virus Trafficking in Infected HepatocytesR01AI080703 · NIAID · UNIVERSITY OF CHICAGO · PI RANDALL, GLENN C · 2010 to 2014
$1.7M
HEPATOCYTE REMODELING BY HEPATITIS C VIRUSR01DK102883 · NIDDK · UNIVERSITY OF CHICAGO · PI RANDALL, GLENN C · 2015 to 2018
$1.4M
High-Throughput Assay for the Discovery of Small Molecule Inhibitors of microRNAR21NS073068 · NINDS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI DEITERS, ALEXANDER · 2010 to 2011
$186k
NIAID NIH HHS R01 AI080703NIDDK NIH HHS R01 DK102883NINDS NIH HHS R21 NS073068
6 · The paper itself

Abstract

MicroRNAs (miRNAs) are noncoding RNA molecules of 22-24 nucleotides that are estimated to regulate thousands of genes in humans, and their dysregulation has been implicated in many diseases. MicroRNA-122 (miR-122) is the most abundant miRNA in the liver and has been linked to the development of hepatocellular carcinoma and hepatitis C virus (HCV) infection. Its role in these diseases renders miR-122 a potential target for small-molecule therapeutics. Here, we report the discovery of a new sulfonamide class of small-molecule miR-122 inhibitors from a high-throughput screen using a luciferase-based reporter assay. Structure-activity relationship (SAR) studies and secondary assays led to the development of potent and selective miR-122 inhibitors. Preliminary mechanism-of-action studies suggest a role in the promoter-specific transcriptional inhibition of miR-122 expression through direct binding to the liver-enriched transcription factor hepatocyte nuclear factor 4α. Importantly, the developed inhibitors significantly reduce HCV replication in human liver cells.

Indexed as

Hepatitis CLiver NeoplasmsMicroRNAsHepacivirusHumansVirus ReplicationMicroRNAsMIRN122 microRNA, human

Identifiers

PMID36449366
PMCPMC9942140
OpenAlexW4310430884

What Socratic 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 Socratic graph.